Honours | Masters | PhD

Burnet Institute 2020 Student Research Projects DISEASE ELIMINATION Characterising sexual risk among early adopters of HIV pre-exposure prophylaxis (PrEP)

Honours, Masters by Research

Associate Professor Mark Stoové [email protected]

Professor Edwina Wright

In Australia, more than three quarters of new HIV dia

Life Sciences 2

2020 Project Summary Life Sciences

Healthy Mothers, Healthy Babies in Papua New Guinea (PNG): Strengthening surveillance and response through The impact of nutrition, malaria, and other infections on multi-pathogen sero-surveillance ...... 09 pregnant women and infants ...... 03 Discovery of a new drug class for HIV treatment and Vaginal microbiota and birth weight in a low-income prevention ...... 09 setting ...... 03 Vaginal microbiota and HIV susceptibility ...... 09 Immunometabolic changes induced by malaria ...... 03 The relationship between inflammation, metabolism and The impact of malaria control measures on the the risk of opioid overdose ...... 10 acquisition of immunity to malaria ...... 04 New methods for measuring extracellular vesicles in Development of novel vaccines against malaria ...... 04 chronic inflammatory diseases ...... 10

Discovering the mechanisms and targets of immunity Bat antiviral defenses against viruses ...... 10 against malaria ...... 04

Identifying targets and mechanisms of acquired immunity to severe malaria in children ...... 05

Understanding malaria transmission and immunity to inform malaria elimination ...... 05

Refolding of exported proteins in malaria parasites ... 05

Establishing the roles of Plasmodium falciparum merozoite invasion proteins ...... 06

Small molecule inhibition of protein secretion in malaria parasites ...... 06

Exported proteins that assist nutrient uptake in malaria parasites ...... 06

Discovering the targets of drugs that stop malaria parasites invading red blood cells ...... 07

Getting to the heart of cardiovascular disease in HIV .. 07

Developing new diagnostic tests for infectious diseases .. 07

Antibody engineering to study responses mediating protective immunity to malaria and other infectious diseases ...... 08

Novel tools and approaches for malaria elimination .. 08

Novel serological and molecular tools for malaria surveillance and intervention ...... 08

Please note: It is advised that all students include a copy of their most recent CV and official/unofficial academic transcript when contacting potential supervisors.

PROJECTS ARE COLOUR CODED TO THE APPROPRIATE PROGRAM:

Maternal and Disease Behaviours and Healthy Ageing Health Security Child Health Elimination Health Risks 3

2020 Projects Life Sciences

MATERNAL AND CHILD HEALTH DISEASE ELIMINATION Healthy Mothers, Healthy Babies in Vaginal microbiota and birth weight Immunometabolic changes Papua New Guinea (PNG) : The impact in a low-income setting induced by malaria of nutrition, malaria, and other infections Honours, Masters, PhD on pregnant women and infants PhD, Masters, Honours Professor Gilda Tachedjian Dr Ricardo Ataide Honours, PhD [email protected] [email protected] Professor James Beeson Dr Joshua Hayward Dr Clovis Palmer [email protected] [email protected] Associate Professor Jack Richards Dr Michelle Scoullar Dr Paul Agius Dr Elizabeth Aitken Associate Professor Freya Fowkes Dr Philippe Boeuf (Melbourne University) Dr Philippe Boeuf Being born small contributes to 80 per Malaria affects 214 million people annually. Malaria is caused by parasites Being born too small is the biggest risk factor cent of neonatal deaths. The risk of that are transmitted to humans by for neonatal death. In resource-poor regions mortality and morbidity significantly mosquitoes. These parasites invade and globally, pregnant women experience high increases when birth weight falls below replicate inside human red blood cells. rates of malaria, under-nutrition, sexually approximately 3kg. This is underscored by The immune system can attack these transmitted infections (STIs), and other viral the programmatic low birth weight (LBW) parasites and the better the immune and bacterial infections, which can lead cut-off of 2.5kg, which the World Health response, the better the clinical outcome to maternal morbidity and mortality and in Organization has targeted for a 30 per for the patient. Monocytes and Neutrophils infants, low birth weight (LBW) resulting in a cent reduction by 2025. are very effective cells that can find and significant number of infant deaths. In these eliminate parasites that are circulating or settings, LBW is due to fetal growth restriction Burnet Institute’s Healthy Mothers, are sequestered. and preterm delivery. However the link Healthy Babies (HMHB) program seeks to identify preventable causes of LBW, between nutrition, malaria, STIs, and other Understanding how metabolic processes infections on birth outcomes is unknown. with the ultimate goal of designing interventions to improve neonatal heath contribute to the activation of immune cells, and the ways used by pathogens Burnet’s research program, Healthy Mothers, and mortality. to modify this activation, has become a Healthy Babies, in partnership with the PNG major focus of research in recent years Institute of Medical Research, East New The HMHB program is an observational with very significant findings in fields Britain Provincial Government, University of prospective cohort study in PNG, as diverse as HIV, TB and Dengue. The PNG, the National Department of Health, and comprising 700 pregnant women and immunometabolism of macrophages others, has undertaken a longitudinal study their babies, from their first antenatal and neutrophils– or the metabolic of 700 pregnant women attending antenatal visit to one-year postpartum. The changes that occur during activation – care, and followed them through to delivery. composition of the vaginal microbiota of have not been studied in the context of Among these women, we will measure markers pregnant women is now recognised as malaria infection. of nutrition and evaluate micronutrient a racially- and geographically-variable determinant of the health of mothers deficiencies, determine malaria and STIs. We This project aims to characterise, in vitro, are also using new powerful metabolomics/ and their babies. Vaginal microbiota may be described as ‘non-optimal’ and the metabolic responses of Monocytes and proteomic approaches to identify nutritional Neutrophils to parasite-derived antigen. and inflammatory markers that may contribute associated with genital inflammation and adverse sexual and reproductive health For your Honours project you will focus to poor pregnancy outcomes, especially low primarily on the metabolism of glucose – birth weight. The association of nutrition, outcomes, compared to ‘optimal’ vaginal microbiota (McKinnon et al 2019 AIDS Res the uptake of glucose, its consumption, malaria, STIs, inflammation and other factors levels of by-products of the glycolytic during pregnancy with pregnancy outcomes Hum Retroviruses). Projects are available to characterise the vaginal microbiota of pathway, the expression of receptors (low birth weight, pre-term delivery, anemia) associated with the uptake of Glucose to will then be assessed. pregnant women in PNG and its stability following birth and the role of the vaginal the cell and the functionality of these cells after exposure. In this project, you will The objective is to determine the major microbiota in modulating birth weight use techniques as diverse as parasite and preventable causes of poor maternal health using next generation sequencing and human cell culture, ELISA, Western Blot, and LBW to enable the development of computational biology. Flow-Cytometry and qRT-PCR. future interventions to improve health and pregnancy outcomes. This project is offered as a laboratory or epidemiological project, or a combination of the two.

FOR MORE INFORMATION GO TO burnet.edu.au 4

2020 Projects Life Sciences

The impact of malaria control Development of novel Discovering the mechanisms measures on the acquisition vaccines against malaria and targets of immunity of immunity to malaria against malaria Honours, Masters, PhD Honours, PhD Honours, PhD Professor James Beeson Professor James Beeson [email protected] Professor James Beeson [email protected] [email protected] Dr Gaoqian Feng Associate Professor Freya Fowkes Dr Herbert Opi Development of a highly effective vaccine Associate Professor Leanne Robinson against malaria is greatly needed for Dr Linda Reiling Malaria caused by Plasmodium falciparum global elimination of malaria. However, Antibodies are an important component remains a major cause of morbidity currently this is hindered because of a of acquired immunity against malaria, as and mortality globally. It has decreased limited knowledge of the mechanisms and demonstrated in pivotal studies in which substantially over the past decade due specific targets of immunity to malaria. We immunoglobulin G (IgG) from immune adults to increased control measures and have used a wide range of approaches to was transferred to malaria-infected children access to efficacious treatments. People identify mechanisms involving antibody and resulted in clearance of infection. The living in Papua New Guinea are less interactions with Fc-receptors, immune mechanisms of protection and specific target exposed to malaria over time due to cells, and complement, and antibody epitopes of protective immunity are not well declining transmission. blocking of receptor-ligand interactions, understood, yet this knowledge is crucial for which may be crucial for effective developing highly effective vaccines against Naturally-acquired blood-stage immunity against malaria. malaria. In recent studies, we have begun to immunity develops to malaria after This project will use our recently uncover important roles for antibodies that repeated exposure that controls blood- can directly inhibit host-cell infection, interact stage parasitaemia, thereby reducing developed technologies and approaches to identify targets and epitopes that with immune cells to kill and clear malaria, or clinical symptoms and life-threatening recruit complement to neutralise infection. complications. Antibodies are important induce functional antibodies. The project mediators of this acquired immunity, will focus on key antigens expressed by The aims of this project include identifying however, it is unclear how declining malaria during its initial invasion stage. key targets of protective immunity (specific malaria transmission impacts on the The project will involve the use of multiple antigens and epitopes) and the quantifying acquisition and maintenance of cellular, molecular, and antibody assays the importance of specific mechanisms malarial immunity. to identify potential targets that could be mediating immunity. This knowledge is included in vaccines. Studies will also crucial for the development of effective The overall objective of this project is investigate the optimal combinations of vaccines against malaria. The project to quantify the impact of changes in antibody targets that induce functional may combine detailed studies of immune malaria transmission on the acquisition immunity in a synergistic manner, and responses with clinical and population and maintenance of malarial immunity in using this knowledge for informing studies in Africa, Asia, and Papua New different malaria endemic populations. vaccine design and the expression and Guinea. It will examine how immune testing of novel vaccine candidates to responses protect children from malaria, Laboratory techniques will include ELISA achieve high levels of protection from or protect pregnant women and their and functional antibody assays and/ malaria. developing babies from the devastating or epidemiological analyses. Findings consequences of malaria in pregnancy. will help us understand how immunity This project is suitable for a student with develops and is maintained against a keen interest in humoral and cellular The studies would particularly focus on malaria and other infectious diseases. immunology and vaccine development. using innovative approaches to understand The student will acquire unique skills how antibodies neutralise and clear malaria in performing immunoassays including parasites in the blood, including interactions ELISA, monocyte/neutrophil isolation, with monocytes/macrophages, neutrophils, flow-cytometry and immune-fluorescent and dendritic cells, and identifying specific staining, phagocytosis assays, as well as epitopes targeted by protective antibodies. standard techniques in cell culture and Skills may involve assays of functional analysing data from population studies. immunity, cell culture, isolation and analysis The specific activities and focus of the of immune cells, flow cytometry, western project will be refined to suit the interests blotting, ELISA, and epitope mapping. The and training background of the student. project will be tailored to best match the student’s interests and training background. 5

2020 Projects Life Sciences

DISEASE ELIMINATION Identifying targets and Understanding malaria Refolding of exported proteins in mechanisms of acquired immunity transmission and immunity to malaria parasites to severe malaria in children inform malaria elimination Honours Honours, PhD Honours, PhD Dr Paul Gilson Professor James Beeson Professor James Beeson [email protected] [email protected] [email protected] Dr Hayley Bullen Dr Jo-Anne Chan Associate Professor Freya Fowkes Mr Mikha Gabriela Dr Jo-Anne Chan Malaria caused by Plasmodium falciparum Malaria is still one of the world’s most is a leading cause of mortality and morbidity Malaria transmission in populations important infectious diseases. Despite a globally, particularly among young children. halving in the impact of malaria over the After repeated exposure, individuals involves interactions between infection rates and prevalence that drive last 10 years, the emergence of multi-drug develop effective immunity that controls resistant parasites is a major threat to blood-stage parasitaemia, thereby reducing transmission, and the presence of malaria immunity that has the potential to reduce further advances. There is an urgent and clinical symptoms and life-threatening ongoing need for the development of new complications. Antibodies are important transmission. Malaria immunity can act to reduce infection rates and levels of malaria antimalarial drugs, especially compounds mediators of this acquired immunity. The that have completely novel mechanisms demonstration that naturally acquired parasitemia, and specific components of immunity can also function to directly of action from those currently in use, antibodies are associated with protection and compounds that simultaneously from malaria is one of the criteria used to block transmission of malaria. This is known as transmission-blocking immunity. target the two major causative agents objectively prioritise malaria antigens for of malaria Plasmodium falciparum and malaria vaccine development. Currently, very little is known about the P. vivax. One highly potent novel target We have recently completed a case-control interactions between malaria infection is the pan-Plasmodium protein export study of severe malaria in children living on rates and patterns and malaria immunity trafficking complex known as PTEX, the north coast of Papua New Guinea. Cases in populations, and how these interact. originally identified by our team. We have were identified at Madang General Hospital Malaria control programs face the demonstrated that PTEX is obligatory and were defined as having severe malaria challenge that as malaria transmission for parasite growth, indeed even mild according to the World Health Organization declines, malaria immunity also declines, perturbation of PTEX function rapidly criteria. Each case of severe malaria which places the population at higher risk kills parasites in the blood. The PTEX was matched to a healthy community of malaria transmission and complex forms protein translocating pores control. Blood samples were taken from rebound epidemics. around intracellular parasites through which parasite proteins gain access to cases at the time of hospital admission This project will investigate the impact and when the patient had recovered. For the cytoplasm of their erythrocyte hosts. of malaria immunity on malaria infection Exported proteins modify their erythrocyte controls, samples were taken at the time of rates and transmission of malaria in enrolment into the study. The project will cells enabling parasites to reproduce and populations. The student will analyse avoid host immunity. determine levels of antibodies to a range various parameters to define the patterns of malaria antigens, and specific epitopes of infection and immunity, with a particular One aspect of protein translocation by Enzyme-linked immunosorbent assay focus on defining the interaction between that is little understood is how the (ELISA) and flow cytometry, and evaluating immunity and malaria transmission. exported proteins are refolded after functional antibody activity, including direct they are extruded into the erythrocyte neutralisation, complement activation, and The findings of this project will be compartment by PTEX. Some form of opsonic phagocytosis. The levels of these highly relevant to informing malaria refolding is presumably required to antibodies and functional activities will elimination efforts and understanding functionally activate exported proteins then be related to clinical outcome using the value of incorporating vaccines into so they can perform their roles. In this statistical analysis including regression elimination strategies. Skills acquired project we aim to trap exported reporter techniques. may include established high-throughput proteins in the process of being exported immunoassays, assays that quantify the These findings will help us understand while protein refolding factors are at work functional activity of immune responses attempting to refold their client proteins. how immunity contributes to protection (e.g. flow cytometry, Fc-receptor mediated from severe malarial disease progression. These refolding proteins will then be immunity, complement activation, western captured and identified so their functions The findings are valuable for advancing blots, ELISA, neutralisation assays). This vaccine development by providing evidence can be investigated by reverse genetic could be expanded to include modelling and chemical approaches. Laboratory supporting certain malaria antigens as of the interaction between infection and targets of protective immunity. techniques will include parasite culture, immunity, and how this may impact on protein purification, mass spectrometry malaria elimination and control. and parasite molecular biology. 6

2020 Projects Life Sciences

Establishing the roles of Small molecule inhibition of protein Exported proteins that assist Plasmodium falciparum merozoite secretion in malaria parasites nutrient uptake in malaria parasites invasion proteins Honours Honours Honours Dr Paul Gilson Dr Paul Gilson Dr Paul Gilson [email protected] [email protected] [email protected] Dr Hayley Bullen Dr Hayley Bullen Dr Hayley Bullen Ms Madeline Dans Ms Thorey Jonsdottir Dr Betty Kouskousis Malaria remains a major global health burden Malaria remains one of the most devastating Mr Chad Johnson causing hundreds of millions of debilitating infectious diseases of humans claiming the infections per year that tragically result in lives of roughly 400,000 people every year. About 40 per cent of the world’s population, nearly half a million deaths. The mosquito Malaria is caused by large-scale infection of the mostly children and pregnant women, are at borne Plasmodium parasites which cause blood with Plasmodium parasites. There is no risk of malaria. Malaria vaccines offer the hope malaria, grow inside in human hepatocytes sterilising vaccine and currently the parasite has of long-term disease control and elimination, and erythrocytes. Although the parasites can developed resistance to all anti-malarial drugs but thus far highly effective vaccines have be eliminated with drugs, they eventually available. Although a lot has been achieved in not been developed despite much effort. The develop resistance, including to the latest malaria control over the past decade, progress most effective RTS, vaccine produced to date frontline artemisinin therapies. Currently has been at a standstill since 2016 and thus halves the occurrence of severe disease for there is no replacement for artemisinin and it is vital to identify new parasite drug targets. about one year in young children by targeting it is crucial that new drugs be identified soon Fundamental to the parasite’s survival in the the sporozoite parasite form that enters the since it can take many years for these to blood stage is its ability to export hundreds of body during mosquito bite. There is a need reach the clinic. A potential new drug target its proteins into the host erythrocyte through a to find additional vaccine antigens that block is the machinery used by parasites to move novel protein translocator called PTEX. These the downstream parasite forms that produce proteins around its cytoplasm and organelles exported proteins act as renovators of the host large-scale infection of the blood which causes and even into the human cells in which they cell to accommodate the growing parasite. symptomatic malaria disease. Merozoites grow. Parasites export hundreds of effector Host cell renovations include the formation are extracellular parasite forms that invade proteins particularly into their erythrocytes, of unusual channels in the erythrocyte erythrocytes where the parasites grow and and these effectors aid nutrient acquisition to membrane termed the new permeability produce more merozoites. Merozoite surface fuel rapid growth and help the parasite avoid pathways (NPPs), which allow influx of essential proteins support erythrocyte entry and are host immunity. We have recently discovered a plasma nutrients and efflux of toxic waste. The considered ideal vaccines since antibodies transporter complex called PTEX that exports molecular machinery involved in creating the that block these proteins could directly inhibit effector proteins into the host cell and have NPPs is unknown. Recently we have provided invasion or recruit immune factors to destroy genetically stopped its expression which led the first genetic proof that the parasite RhopH the merozoites. This project aims to follow to rapid parasite death. This validates PTEX protein complex is critical for NPP activity four different proteins involved in merozoite as an important drug target along with the and that blocking the function of the RhopH invasion and resolve their order of action to protein trafficking machinery that delivers complex halts parasite growth and replication. understand their invasion functions. This will effectors to PTEX. To identify novel protein RhopH2 is one of three proteins constituting be achieved by tagging the genes for invasion transport inhibitors the Honours project will the RhopH complex and we have shown that proteins with tags for green fluorescence involve screening the MMV Pathogen Box it binds several other exported proteins. These protein (GFP) and the glmS riboswitch using of parasite inhibitors for compounds that accessory proteins could be directly involved the CRISPR/Cas9 system. GFP will permit the reduce protein secretion and export. This in NPP functions or could help assist in the location of these proteins to be visualised screen will involve plate-based assays to transport and assembly of the RhopH complex. during live invasion microscopy imaging detect if the inhibitors block the trafficking of that will help define the proteins’ roles. The bioluminescent marker proteins. The activity This project will investigate the role of the RhopH riboswitch will enable expression of the of potential trafficking inhibitors will be binding proteins by installing genetic switches invasion proteins be switched off so the effects validated by microscopically monitoring their on their genes using CRISPR/Cas9 technology, of protein loss on invasion can be studied. effects in parasites expressing fluorescent which will enable the genes to be switched Laboratory techniques will include parasite marker proteins. Newly discovered trafficking off and protein functions can be studied. A culture, plasmid cloning, parasite transfections inhibitors could be further considered for better understanding of how parasites regulate and live microscopy. A greater understanding future optimisation towards pre-clinical nutrient uptake could lead to novel ways of of when merozoite proteins are deployed uptake. Laboratory techniques learned will blocking this vital process and prevent parasite on the parasite cell’s surface and improved include tissue culturing, parasites growth growth. Laboratory techniques will include knowledge of their biological function could experiments, assay development and parasite culture, plasmid cloning, parasite help prioritise which proteins should be fluorescence microscopy. transfections, molecular biology and nutrient developed into future vaccines. uptake assays. 7

2020 Projects Life Sciences

DISEASE ELIMINATION Discovering the targets of drugs Getting to the heart of Developing new diagnostic tests that stop malaria parasites cardiovascular disease in HIV for infectious diseases invading red blood cells Honours Honours, Masters, PhD Honours Dr Anna Hearps Associate Professor Jack Richards Dr Paul Gilson [email protected] [email protected] [email protected] Dr Janine Trevillyan (Alfred Hospital) New tests are required to diagnose Dr Hayley Bullen infectious diseases in resource-poor Professor Jenny Hoy (Alfred Hospital) Ms Madeline Dans settings to enable prompt treatment Despite effective therapy that suppresses HIV and to strengthen public health disease Malaria caused by the blood-stage of replication and prevents AIDS, people living with surveillance. A wide range of projects Plasmodium falciparum, remains a major HIV (PLWH) suffer an increased risk of a number are available to develop new diagnostic global health problem with about 40 per cent of co-morbid conditions including heart disease, tests with technologies including lateral of the world’s population at risk of infection. which is now one of the greatest causes of flow cartridges for point-of-care testing, Although there have been major reductions disease and death in PLWH on anti-HIV therapy. isothermal nucleic acid amplification in disease impact over the last 10 years due HIV+ individuals have over twice the risk of for high sensitivity testing, and to increased malaria control, this downward developing cardiovascular disease as compared high-through put serological assays for trajectory has recently stalled. Of particular to the general population, but why this population-based surveillance. This concern is the spread of multi-drug resistant occurs is still unknown. A number of possible includes developing tests against malaria, parasites in regions of Asia, including to mechanisms have been proposed including a) viral hepatitis, sexually-transmitted artemisinin combination therapies, the systemic inflammation and immune activation diseases and a range of other infectious current frontline treatments. This emphasises that persist despite effective anti-HIV therapy, diseases. Projects can be tailored to the critical need to discover novel drug b) increased platelet activation as a side your interests. targets with different and known mechanisms effect of anti-HIV medications or c) altered Projects will involve laboratory experience of action (MoA) to produce highly potent function of cells which drive the early stages in developing new diagnostic tests, treatments refractory to resistance. After the of cardiovascular disease (eg monocytes). validation of tests with clinical samples invasive merozoite parasite stage invades a There is evidence that the pathogenesis of and field studies, engagement with red blood cell (RBC) the parasite grows and cardiovascular disease in PLWH may differ industry partners, and the processes of replicates to yield ~20 new merozoites that subtly to the general population, which has commericalisation. egress from the old RBC to infect new cells. implications for how to best predict, prevent and This exponential amplification of infected treat this disease in the HIV+ population. RBCs results in symptomatic malaria and as such merozoites are an ideal therapeutic We are collaborating with clinician-researchers target since any new drug or vaccine that located onsite at the Alfred Hospital to could block merozoite invasion would investigate a number of these critical questions dramatically reduce the parasite load. This including: project will involve discovering the MoA of several invasion inhibiting drugs identified 1. Can we identify biomarkers that predict a in a library of parasite killing compounds cardiovascular event in PLWH? called the MMV Malaria Box. Bioluminescent 2. What is the best way to identify early parasites treated with the MMV compounds cardiovascular disease in PLWH? will be assayed to discover which step in the complex egress and RBC invasion process is 3. How effective are treatments used in being blocked. Live cell imaging of invading the general population at preventing merozoites will be further performed to cardiovascular disease in PLWH? validate which invasion step is being affected by the MMV compounds. Finally, 4. Do co-infections with other pathogens in parasites will be repeatedly treated with the addition to HIV potentiate the development MMV compounds to attempt to select for of cardiovascular disease? genetic resistance in genes for the target proteins of the drugs. If time permits target These projects involve a range of laboratory gene mutations will be identified through techniques (ie ELISA, cytokine measurements, genome sequencing. Laboratory techniques cell culture, molecular biology), data analysis/ learned will include tissue culturing, parasites statistics and clinical epidemiology and can growth experiments, assay development and be tailored depending on the interest of the fluorescence microscopy. individual student. 8

2020 Projects Life Sciences

Antibody engineering to study Novel tools and approaches for Novel serological and molecular responses mediating protective malaria elimination tools for malaria surveillance and immunity to malaria and other intervention infectious diseases Honours, Masters, PhD Honours, Masters, PhD Associate Professor Jack Richards Honours, Masters, PhD [email protected] Associate Professor Leanne Robinson Associate Professor Jack Richards Dr Ricardo Ataíde [email protected] [email protected] Current efforts to sustain malaria control Malaria elimination is a global and advancement towards elimination Antibodies are key effector molecules commitment that is achievable, but are being hindered by an increase in the responsible for mediating protection will require the development of novel proportion of asymptomatic infections against many other infectious diseases. tools and approaches. This project will with densities too low to be detectable This project will involve engineering include engaging with local communities by standard diagnostic tools. These novel recombinant antibodies against and stakeholders in malaria-endemic infections escape routine detection malaria parasite proteins and those of countries to understand practical and treatment but have the potential to other infectious diseases organisms. challenges and needs. It will involve sustain transmission. The lack of tools These will then be used in a range of in establishing mapping and surveillance to accurately, rapidly and cost-effectively vitro immunological assays to determine tools so that hotspots of transmission identify the reservoirs of ongoing their precise functional mechanisms and can be identified in real time, and transmission for targeted interventions efficacy in protective immunity. therefore enable targeted responses to is thus a major roadblock to achieving the areas and people that are most in These studies will be used to develop malaria elimination. novel therapeutics and to guide vaccine need. This will include establishing high- development. precision geospatial mapping and spatial We have developed and validated novel decision support systems that can guide molecular assays capable of detecting interventions ultra-low density Plasmodium infections and monitor the effectiveness of and serological assays capable of responses. specifically identifying individuals with recent exposure to malaria infection. It’s aimed to broaden the focus on These screening tools offer the potential malaria elimination activities in the to detect and understand transmission Asia-Pacific to bring health benefits for dynamics at a depth that was previously a range of other infectious diseases impossible. (e.g. vaccine-preventable diseases, blood-borne viruses, other vector-borne This project will involve validating the diseases). These projects can be tailored ability of these tools to track malaria to specific student interests. transmission foci across a range of transmission settings in Papua New Guinea, Solomon Islands, Thailand and Cambodia. This will involve conducting both laboratory based molecular and serological assays and epidemiological data analysis and interpretation.

The findings of this project will be highly relevant to informing malaria elimination efforts and developing evidence-based surveillance strategies to take forward into novel implementation trials. 9

2020 Projects Life Sciences

DISEASE ELIMINATION Strengthening surveillance and Discovery of a new drug class for Vaginal microbiota and HIV response through multi-pathogen HIV treatment and prevention susceptibility sero-surveillance Honours Honours, PhD Honours, PhD, Masters Professor Gilda Tachedjian Professor Gilda Tachedjian Associate Professor Leanne Robinson [email protected] [email protected] [email protected] Dr David Chalmers Dr Anna Hearps Serological screening to detect previous Dr Joshua Hayward Dr Joshua Hayward exposure to infections through measuring Dr Raffi Gugasyan antibody responses can play a key There is a real threat that drug resistance, role in surveillance as a public health toxicity and intolerance will eventually HIV transmission is modulated by the intervention. Recent developments in lead to exhaustion of antiretroviral drug vaginal microbiota. Women colonised high-throughput multi-plex technologies options for both HIV treatment and with optimal vaginal bacterial enable the simultaneous measurement of prevention, especially since there is communities have a decreased risk of antibody responses to multiple antigens little in the way of new drug classes in acquiring and transmitting HIV compared using very small volumes of plasma that the pipeline. We have initiated a drug to women colonised with non-optimal can be extracted from dried blood spots. discovery program targeting HIV-1 reverse microbiota such as bacterial vaginosis The optimisation and application ofmulti- transcriptase (RT) to identify compounds (BV) a common condition in women of pathogen (e.g. dengue, chikungunya, that inhibit this essential enzyme. We reproductive age. BV is characterised by malaria, lymphatic filariasis, measles, are using an innovative and a validated depletion of beneficial Lactobacillus spp. helminths, leptospirosis) serological paradigm for drug discovery called and high relative abundance or load of screening to sample sets and surveillance fragment-based drug design that uses facultative and/or obligate anaerobes. programs in countries such as Papua very small compounds called ‘fragments’ These microbiota increase local pro- New Guinea, will allow the generation to find inhibitors with novel mechanisms inflammatory cytokines, recruit activated of geo-spatial sero-prevalence maps to of action against HIV-1 RT. HIV target cells and disrupt cervicovaginal inform disease control programs and Our screens have discovered fragments epithelial barrier integrity that drive support decision-making. Optimisation of with mechanisms that are distinct to increased HIV risk. While studies have antigens and algorithms to differentiate other drugs that inhibit HIV-1 RT in the described the association between the between recent exposure and life-time clinic (La et al 2015 PNAS 112:6979) vaginal microbiota and increased HIV exposure depending on setting and and some of these have been progressed susceptibility, relatively little is known relevant pathogens will be a key priority. to molecules that have low micromolar about the function of these microbiota This project will involve laboratory-based activity against wild-type and through the action of their metabolites serological assays, epidemiological data drug-resistant RT. on the genital mucosa and directly on analysis and spatial mapping, providing HIV (Aldunate et al 2015 Front Physiol). A the opportunity to contribute to the The aim of this study is to progress one major distinguishing feature of women development and application of a public of the fragment hits into more potent RT colonised with optimal vaginal microbiota health tool for surveillance and response. inhibitors or drug leads. Compounds are compared to women with BV is a dramatic structurally related to the fragment hit increase in the levels of lactic acid and will be evaluated for their ability to bind depletion of short chain fatty acids and inhibit wild-type and drug-resistant suggesting a role for these metabolites as RT, as well as inhibit HIV-1 replication. effector molecules produced by vaginal bacteria. This study will identify leads for the development of a novel class of RT Projects are available to determine inhibitor for use in HIV-1 treatment and the direct anti-HIV mechanism of prevention. This is a joint project between vaginal microbiota metabolites, and the Tachedjian Lab and Monash Institute their immune modulatory and barrier of Pharmaceutical Sciences. modulating effects on vaginal epithelial cells underpinned by RNAseq data (Hearps et al 2017 Mucosal Immunol). These studies will inform development of interventions to target BV to prevent adverse sexual and reproductive health outcomes.

FOR MORE INFORMATION GO TO burnet.edu.au 10

2020 Projects Life Sciences

BEHAVIOURS AND HEALTH RISKS HEALTHY AGEING HEALTH SECURITY The relationship between New methods for measuring Bat antiviral defenses against inflammation, metabolism and the extracellular vesicles in chronic viruses risk of opioid overdose inflammatory diseases Honours Honours Honours, PhD, Masters Professor Gilda Tachedjian Dr Anna Hearps [email protected] Dr Philippe Boeuf [email protected] [email protected] Dr Joshua Hayward Associate Professor Anthony Jaworowski Professor Paul Dietze (RMIT University) Bats are a major reservoir of viruses such Professor Mark Stoové as Ebola virus that are pathogenic in Mr Steven Lim (AMREP Flow Cytometry) humans but not in bats. The reason bats Professor James Beeson can coexist with these viral pathogens is Extracellular vesicles (EV) are small unknown. The role of the host’s immune Opioid overdose is a significant public health (<1µm) membrane-bound particles system is to control infections and host problem and has increased recently, with which are released from different cellular restriction factors are the front line of people who inject drugs particularly at risk of compartments and can carry a variety the innate immune response that target overdose. However, a substantial percentage of different protein and nucleic acid viruses. These factors have originally of those who inject opioids do not experience cargoes. They play an important role in been discovered to restrict retroviruses overdose, suggestive of personal and normal intercellular communication, but from other mammalian species, such biological risk factors. their number and type can be altered in as HIV (Hayward et al 2018 Mol Biol Evol a range of pathological conditions. As 35:1626), and some of these factors e.g. Known risk factors include dose and route of such, EVs are gaining much attention for tetherin, can restrict paramyxoviruses opioid intake as well as concomitant use of use not only as diagnostic biomarkers and filoviruses. While bats harbour many alcohol or benzodiazepines. The biological for various disease states but also as diverse viral species, retroviruses are yet bases for these associations are not known. potential mediators of the disease to be isolated from bats. Endogenous themselves. We have a particular interest However, some of these risk factors could retroviral sequences are present as a in EVs generated during HIV infection and be linked with chronic inflammation and critical part of eukaryotic genomes and healthy ageing, and the extent to which metabolism. For example, chronic alcohol normally represent the fossil record they persist and contribute to immune misuse is pro-inflammatory whereas of extinct viruses. Our analysis of the dysfunction and disease. The analysis benzodiazepines have anti-inflammatory genome of bat species reveals the of EVs is challenged by their small size, properties and will differentially influence presence of retroviral sequences that but newer technologies such as imaging metabolism. This suggests that inflammation demonstrate homology to currently flow cytometry offer a new and potentially and metabolism may be central risk factors existing gammaretroviruses and improved method for visualising these for opioid overdose. Furthermore, chronic betaretroviruses (Hayward et al 2013 particles. inflammation and altered metabolism would Retrovirology 10:35) indicating that increase the risk of additional chronic disease This project aims to establish techniques retroviruses have circulated in bats. and impact on overall health. Taking a unique to measure and characterise EV generated However, whether infectious retroviruses biological approach to a public health issue, by HIV using the AMNIS ImageStream are currently circulating in bats is we hypothesize that inflammation and altered imaging flow cytometer. These techniques unknown. We have discovered retroviral metabolism are major risk factors for opioid will be used to study EV secreted from sequences in bat scat that we engineered overdose and related to poor overall health. HIV-infected cells and also in stored into a replication-competent virus. plasma samples from healthy ageing and This study will focus on characterising The student will use a combination HIV cohort studies. These experiments the ability of a class of bat restriction of multiplex ELISA and cutting-edge will lead to future studies using factors to inhibit the replication of our metabolomics approaches to quantify a retrospective cohorts with stored plasma engineered bat retrovirus. This is a joint broad range of inflammatory markers and samples to investigate the association project between the Tachedjian Lab and metabolites in plasma/serum samples between EVs, disease outcomes such as CSIRO AAHL. collected from people who inject drugs. They HIV disease progression, cardiovascular will use biostatistical approaches to control disease and other inflammatory for known risk factors for overdose to identify conditions. markers associated with opioid overdose as well as potential causes of this inflammation This is a laboratory-based project which and metabolic disturbances.This innovative involves the following techniques: project could lead to interventions aimed imaging flow cytometry, cell culture, at reducing inflammation and restoring EV isolation, ELISAs. metabolism in people who inject drugs in order to curb the rising rate of opioid overdose. Public Health 12

2020 Project Summary Public Health

Vaginal microbiota and birth weight in a low-income Why do some people with hepatitis C continue to drink? ... setting ...... 13 ...... 18

Malaria drug resistance in the Asia Pacific region ...... 13 The role of social influence in opiate substitution therapy ...... 18 Using mathematical models to reduce malnutrition among children in low -income countries ...... 13 Inflammation as risk factor for opioid overdose ...... 19

Understanding perceptions of sexual risk in the era of Using simulation modelling to perform alcohol policy biomedical prevention ...... 14 experiments ...... 19

Exploring reasons to start, stop, and take a break from HIV The potential of naloxone to reduce opioid overdose pre-exposure prophylaxis ...... 14 deaths: modelling the impact of broader distribution .... 19

Management of hepatitis C disease outbreaks using Analyzing the impact of the North Richmond supervised mathematical modelling ...... 14 injecting room using data from a cohort study of people who inject drugs ...... 20 Evaluating the effectiveness and cost-effectiveness of interventions to eliminate infectious diseases ...... 15 Evaluating health promotion strategies targeting alcohol and other drug use among the South Sudanese community Understanding HIV-positive patients with Hepatitis C virus in Melbourne ...... 20 (HCV)-coinfecton trajectories through HCV care ...... 15 Understanding ‘never overdosing’ in a cohort of people Alcohol advertising on public transport: Level of exposure who inject opioids ...... 20 among children and young people ...... 15 Social networks of people who use drugs ...... 21 Mapping public injecting drug use in urban Melbourne ... 16

Qualitative analysis of reasons for insufficient levels of individual needle and syringe coverage ...... 16

Sex, drugs and rock’n’roll: Young people and risk behaviours ...... 16

Sexting, porn, and Tinder: An investigation of education and health promotion ...... 17

The outcomes of transitioning between prison and community for people with a history of injecting drug use ...... 17

The persistence of risk among people who inject drugs .. 17

Understanding risky single occasion drinking and links to harms in a cohort of young Melburnians ...... 18

Please note: It is advised that all students include a copy of their most recent CV and official/unofficial academic transcript when contacting potential supervisors.

PROJECTS ARE COLOUR CODED TO THE APPROPRIATE PROGRAM:

Maternal and Disease Behaviours and Healthy Ageing Health Security Child Health Elimination Health Risks 13

2020 Projects Public Health

MATERNAL AND CHILD HEALTH Vaginal microbiota and birth weight Malaria drug resistance in the Asia Using mathematical models to in a low-income setting Pacific region reduce malnutrition among children low -income countries Masters Honours Honours, PhD Dr Paul Agius Associate Professor Freya Fowkes [email protected] [email protected] Dr Nick Scott Professor Gilda Tachedjian Professor James Beeson [email protected] [email protected] Associate Professor Leanne Robinson Malnutrition is responsible for over three Dr Joshua Hayward million child deaths each year with 36 Malaria is a major global health issue countries carrying the bulk of the burden. Dr Philippe Boeuf causing around 300 million cases and There are proven community-based 500,000 deaths annually. In recent years Being born small contributes to 80 interventions to target malnutrition; we have witnessed the alarming spread per cent of neonatal deaths. The risk however, resources are limited, so funds of resistance to many drugs used to treat of mortality and morbidity significantly must be allocated to programs that malaria, and this is compromising malaria increases when birth weight falls below achieve the maximum impact. control and elimination efforts and may ~3.0 kg. This is underscored by the be contributing to increasing rates of programmatic low birth weight (LBW) Optima Nutrition is a mathematical model malaria in some regions. The emergence cut-off of 2.5 kg, which the WHO has that quantifies the benefits of providing and spread of drug resistance has been targeted for a 30 per cent reduction by nutrition-based interventions to children particularly concerning in the South East 2025. Burnet Institute’s Healthy Mothers, under five. The model incorporates risk Asia region, and controlling the spread of Healthy Babies (HMHB) program seeks factors for malnutrition among children drug resistance has been a major global to identify preventable causes of lower including low birthweight and/or preterm activity. Understanding the prevalence of birth weight, with the ultimate goal birth, rates of exclusive breastfeeding resistance to different antimalarial drugs of designing interventions to improve and the incidence of diarrhoea. When and tracking the spread of resistance is neonatal heath and mortality. The HMHB a user changes the way that funding is essential. program is an observational prospective allocated between interventions or the cohort study in Papua New Guinea, total amount of money that is available, This project will quantify drug resistance the model projects how this will impact comprising 700 pregnant women and to antimalarial drugs currently in use their babies, from their first antenatal stunting, wasting, anaemia and mortality in Papua New Guinea and/or Myanmar among children under five. The model visit to one year postpartum. The using samples from large clinical and composition of the vaginal microbiota of is able to determine how a designated population studies. PCR and other budget can be optimally allocated pregnant women is now recognised as molecular methods will be used to a racially- and geographically-variable between a set of programs to produce the quantify drug resistance markers for best overall outcomes. determinant of the health of mothers artemisinin, sulfadoxine-pyremethamine, and their babies. Vaginal microbiota lumefantrine, piperaquine, and This project will involve applying may be described as ‘non-optimal’ and chloroquine, and will be combined the Optima model to a specific associated with genital inflammation and with statistical analysis and geospatial low-income country in the Pacific Region. adverse sexual and reproductive health mapping of resistance, depending on This research will require quantitative outcomes, compared to ‘optimal’ vaginal the student’s specific interests and data analysis, with data drawn from microbiota (McKinnon et al 2019 AIDS Res training. The project will determine the the literature, population surveys and Hum Retroviruses). Projects are available extent of drug resistance in populations, economic analyses. The project to characterise the vaginal microbiota of comparing different regions, and evaluate will produce practical policy pregnant women in PNG and its stability changes in drug resistance over time. recommendations for following birth and the role of the vaginal nutrition programming. microbiota in modulating birth weight by developing and using statistical methods to address the latent (hidden) complexity of the microbiota, not captured by current simplistic hierarchical clustering analysis, and associations with adverse birth outcomes.

FOR MORE INFORMATION GO TO burnet.edu.au 14

2020 Projects Public Health

DIESEASE ELIMINATION Understanding perceptions of Exploring reasons to start, stop, and Management of hepatitis C disease sexual risk in the era of biomedical take a break from HIV pre-exposure outbreaks using mathematical prevention prophylaxis modelling

Honours, Masters Honours, Masters Honours, PhD Dr Kathleen Ryan Dr Kathleen Ryan Dr Nick Scott [email protected] [email protected] [email protected] Professor Mark Stoové Professor Mark Stoové Dr Rachel Sacks-Davis Associate Professor Edwina Wright Associate Professor Edwina Wright The discovery of a hepatitis C (HCV) treatment has the potential to lead to HIV pre-exposure prophylaxis (PrEP) and In Victoria, approximately 300 people disease elimination, with smaller states treatment as prevention (TasP) are two are diagnosed with HIV each year and 75 such as Tasmania (or small countries highly effective biomedical prevention per cent of new HIV diagnoses are such as Iceland) likely to be the first to tools that reduce HIV transmission among gay, bisexual and other men who reach this goal. Once elimination has through the use of antiretroviral therapy. have sex with men. HIV pre-exposure been achieved in these places, it will be Victoria has recorded high uptake of both prophylaxis (PrEP) is a new highly critical to ensure that future outbreaks PrEP and TasP and which is thought to effective HIV prevention tool in which do not occur. The risk of an HCV outbreak have contributed to recent declines in HIV people at risk of HIV take antiretroviral occurring will depend on the social transmission. therapy to prevent HIV acquisition. There network structure among people who has been high uptake of PrEP among inject drugs, the coverage of prevention In addition to impacting HIV Victorian GBM through demonstration interventions and the ways in which transmission, the implementation of studies and this is thought to have injecting equipment is shared. biomedical prevention has shifted contributed to recent declines in HIV the language used in HIV prevention, transmission. The aim of the project is to create an the definition of ‘safe sex’, and other agent-based model of people who inject preventive behaviours. It is important to In April 2018 PrEP was listed on the drugs, including different possible understand these changes so research Pharmaceutical Benefits Scheme and is injecting network structures (e.g. different and health promotion can adapt to recommended for use by all people at social connectedness, nodal degree). current norms. high risk of HIV. While there is significant The model will then be used to simulate data on the efficacy of PrEP, and PrEP the reintroduction of HCV and compare This research project will use a use in clinical trials, less is known about the effectiveness of different policies to combination of survey data and in- why people decide to use PrEP once it detect and contain it, according to which depth interviews with people who have has been approved for use and publicly results in the fewest affected individuals used combinations of HIV biomedical available. Local research into PrEP has and the shortest time period before it prevention to understand how these tools now shifted to explore the real world is controlled. The research output could have impacted their perceptions of risk implementation and impact of PrEP use. for HIV and STIs and negotiating this risk. then dictate decisions and policies on These data will inform our understanding This research project will explore what how to manage infectious diseases. of risk and improve sexual health contributes to an individual’s decision messaging. to start, stop and take a break from PrEP use. The student will use a combination of online survey data and interviews with GBM to understand decisions to use or not use PrEP. The outcomes of this project will refine HIV health promotion messaging and improve PrEP delivery for Victorian GBM.

FOR MORE INFORMATION GO TO burnet.edu.au 15

2020 Projects Public Health

DISEASE ELIMINATION BEHAVIOURS AND HEALTH RISKS Evaluating the effectiveness and Understanding HIV-positive Alcohol advertising on public cost-effectiveness of interventions patients with Hepatitis C virus transport: Level of exposure among to eliminate infectious diseases (HCV)-coinfecton trajectories through HCV care children and young people Honours, PhD Honours, Masters Honours, Masters by Research Dr Nick Scott Dr Megan Lim Dr Daniela van Santen [email protected] megan.lim @burnet.edu.au [email protected] Dr Alisa Pedrana Dr Nick Scott Dr Joseph Doyle Since highly effective treatments for Alcohol advertising is associated Viral hepatitis is responsible for more hepatitis C (HCV) became available in with increased alcohol consumption, deaths globally than HIV and malaria, Australia in 2016, elimination of the particularly among young people. Current with hepatitis C virus (HCV) accounting disease is now a realistic possibility. regulations attempt to limit exposure of for a half of viral hepatitis-related However, many people remain alcohol marketing to children, however, deaths. In 2013, all-oral direct-acting undiagnosed, and elimination will involve no restrictions are in place regarding antiviral (DAA) therapy transformed a concerted effort to find and link them advertising on public transport. to care so that they can be cured before HCV treatment. With only 8–12 weeks of developing liver cirrhosis or liver cancer. treatment, >95% of patients are cured This project will include an audit of So far, many interventions have been of HCV, including HIV/HCV-coinfected alcohol advertising on public transport. implemented to try to increase diagnosis individuals in whom cure rates with prior Basic modelling will be conducted using rates, but it is unclear which ones have interferon-based therapies were <50%. publicly available public transport usage been the most effective because they Compared to HIV-negative populations, data. The project will result in a policy have been implemented simultaneously HCV infection is more prevalent in people document advising on the potential in some locations. This project will use living with HIV (PLWHIV), and mortality level of exposure of children to these mathematical modelling to untangle rates are also 12 times greater. advertisements. these combined effects to determine Whilst PLWHIV have high levels of which interventions have had the linkage to care than their HIV-negative greatest impact. counterparts as part of their routine The project will involve calibrating an HIV visit, not all individuals who are existing HCV model to testing, treatment, prescribed HCV treatment follow the and epidemiological data, all of which course of treatment and may be lost to includes the combined effects of changes follow up. This is particularly worrisome to multiple interventions over time. in PLWHIV as it is known that HIV The model the will then be used to contributes to a faster liver disease simulate counter-factual scenarios where progression and an HCV co-infection can individual interventions did not occur, impact HIV disease progression. Hence to estimate what might have happened understanding which patients fail to in their absence and therefore their initiate treatment or are lost to follow-up effectiveness. Data from the specific is crucial to prevent liver-related disease health services will be analysed to inform progression and on-going transmission in the model and cost of interventions. this group. Interventions will be ranked according Using data from a cohort of HIV-positive to their increase in treatment uptake, gay and bisexual men, this project aims and cost per additional person treated. to understand patients’ trajectories Outcomes of this project will be used to through HCV care, along with socio- inform the response to HCV elimination demographic and behavioral predictors in Australia. of loss to follow up. This study involves quantitative analysis of retrospective data from clinical databases (data already collected).

FOR MORE INFORMATION GO TO burnet.edu.au 16

2020 Projects Public Health

Mapping public injecting drug use Qualitative analysis of reasons Sex, drugs and rock’n’roll: Young in urban Melbourne for insufficient levels of individual people and risk behaviours needle and syringe coverage Honours Honours, Masters by Research Honours, Masters Professor Paul Dietze Dr Megan Lim [email protected] [email protected] Dr Peter Higgs Dr Peter Higgs [email protected] Sexually transmitted infections (STI) Professor Paul Dietze are on the rise among young Victorians. The risks associated with injecting drug Since 2005, we have surveyed over 9,000 use are determined by interactions Australia has an estimated 3000+ people aged between 16 and 29 years age between individual injecting behaviours needle and syringe distribution outlets, at Melbourne’s Big Day Out about sexual and the environment’ (e.g., physical, servicing an estimated population of risk behaviour and drug use. From 2015, social, legislative) in which injecting 90,000 people who inject drugs (PWID), we moved the survey to an online form. occurs. Using a mixed methods approach, or approximately one outlet per 30 Questions have covered participants’ this project will undertake ethnographic PWID. Furthermore, Australia operates sexual histories, condom use, knowledge mapping and quantitative secondary under an unlimited dispensation policy, and perceptions of STIs, and STI testing data analysis to document aspects of whereby PWID can acquire as many histories. We ask about alcohol and public injecting drug use in inner urban needles/syringes as needed, without other drug use, and other risks and Melbourne. The ethnographic mapping the requirement of exchanging unsterile behaviours such as gambling, diet and exercise will involve neighbourhood- syringes; a policy adopted in other exercise, contact with police, mental level observational research to examine countries. health and smoking. There is also a sites of public injecting, levels of public series of questions concerning media use injecting and document associated Despite this comprehensive level of e.g. pornography, sexting, social media, injecting practices and potential risks. service delivery, previous research has smartphones and online gambling. The shown that 16-37% of Australian PWID Additional secondary data analysis will student project could focus on one of do not acquire sufficient needles and these issues or a range of themes. be undertaken to examine indicators of syringes to cover all of their injecting the impacts of public injecting, such as episodes. These findings, in the context of current fatal and non-fatal overdose and impacts public health measures, will be used to on public amenity. This insufficiency leads to known and advise on the design of future sexual documented risk behaviours, such as health promotion campaigns. syringe re-use and receptive syringe sharing which in turn increase the risk of In this project the student will use the disease transmission, bacterial infection data collected to investigate patterns of and vein damage. sexual risk behaviours, knowledge, and attitudes. This will involve quantitative The reasons an individual may fail to analysis of the relationship between acquire sufficient syringes are many variables such as condom use, number and varied. Past research has shown of sexual partners, drug and alcohol use, that levels of service access and perceptions of risk. The project could (eg. opening times), geographical also involve in-depth qualitative data proximity to services, policing practices, collection via focus group discussions and cohesiveness of PWID networks or interview. affect syringe acquisition/distribution. Other work has identified a number of person-level associations with insufficient coverage, such as risky drinking levels and hepatitis C disease status.

However, the personal reasons a person may fail to acquire sufficient syringes is poorly understood. To have greater knowledge of these reasons, the ability of services to better target at-risk groups, to enhance service provision and ultimately, to facilitate PWID to acquire enough syringes will be increased. 17

2020 Projects Public Health

BEHAVIOURS AND HEALTH RISKS Sexting, porn, and Tinder: An The outcomes of transitioning The persistence of risk among investigation of education and between prison and community people who inject drugs health promotion for people with a history of injecting drug use Honours Honours, Masters by Research Professor Paul Dietze Honours, Masters by Research Dr Megan Lim [email protected] [email protected] Professor Paul Dietze Dr Peter Higgs [email protected] Access to new technologies could Professor Mark Stoové present novel risks to young people’s Professor Mark Stoové The prevalence of risk behaviours such sexual health. The emerging popularity Injecting drug use disproportionately of sexting, online pornography use, and as sharing of injecting equipment among contributes to the health and social people who inject drugs (PWID) has been dating apps has been linked in some burden of illicit drug use in Australia. studies to sexual risk behaviours e.g. not well described in the Australian context. Initiation and ongoing injecting drug use However, little is known about transitions using condoms. There is very little known is influenced by a complex interaction of about educating young people about in risk behaviours among PWID over time social, health, structural, and policy factors, and whether Australian PWID moderate these topics. Many previous programs including the ongoing criminalisation of drug have taken a fear-based approach which their behaviours in response to their use and the routine incarceration of people changing circumstances. tends to exaggerate the risks of these for drug-related crime. These factors also behaviours and promote abstinence mean that people who inject drugs (PWID) In this study data from the Melbourne as the only option. This project will are vastly over-represented in the prison and Injecting Drug User Cohort Study (MIX) investigate previous campaigns and broader criminal justice system. Transition will be examined to determine the extent provide recommendations for future out of prison represents a particularly to which risk behaviours change over campaigns. A mixed methods approach vulnerable period for PWID that is time in the cohort and what impact any will involve content analysis and review characterised by challenges associated with changes have on key health outcomes of existing health promotion relating to social reintegration, housing, employment, such as blood borne virus transmission. sexting, pornography, and other new accessing health and other support services, sexual media. and relationships with significant others. Return to dependent patterns of drug use is also common, resulting in very high rates or mortality, morbidity, recidivism and re- incarceration in this population.

Burnet Institute is undertaking Australia’s first prison-to-community prospective cohort study of people with injecting drug histories. This study provides the opportunity for the pre- and post-release analysis of data collected from ~500 participants in the weeks preceding their prison release and in the first three months following their release.

A range of post-release outcomes is available for investigation including but not restricted to patterns of drug use, engagement and retention in treatment and health care, self-report overdose, significant other relationships, housing stability and blood borne virus risk. Univariate descriptive and prospective analyses examining the pre- and post-release predictors of outcomes would be undertaken to describe the burden of various outcomes and their association with exposures to help inform policy and practice in the Justice and Health arenas. 18

2020 Projects Public Health

Understanding risky single Why do some people with The role of social influence in occasion drinking and links to hepatitis C continue to drink? opiate substitution therapy harms in a cohort of young Melburnians Honours, Masters Honours Dr Rachel Sacks-Davis Honours Dr Peter Higgs [email protected] [email protected] Professor Paul Dietze Professor Margaret Hellard [email protected] Professor Paul Dietze Professor Paul Dietze Dr Megan Lim Alcohol use is the strongest known modifiable determinant of HCV disease Opiate substitution therapy is an Young Australians frequently engage in progression. Alcohol consumption has evidence based intervention for reducing risky single occasion drinking (RSOD). been found to raise the viral load and the health risks of addiction to opiates. This drinking pattern is associated with accelerate hepatic fibrosis in the context Among people who inject drugs, it a variety of harms including increased of HCV infection, and heavy alcohol is associated with reduced injecting risk of accidents, exposure to violence consumption is a risk factor for premature frequency, and reduced risk of hepatitis C and risky sex. Most research on RSOD death from HCV. Moreover, as well as and HIV infection. has focused on normative drinking impacting on liver disease progression, The effects of social influence have been behaviours within the past year rather heavy alcohol use may influence the investigated in many aspects of health, than on the specific circumstances of likelihood of successful HCV treatment. including obesity, smoking and drug use; RSOD. The aim of this study is to examine however, few studies have investigated specific occasions of RSOD by young The proposed project involves in-depth the role of social influence on the people to understand the specifics of interviews with up to 25 consenting probability of initiating or continuing drinking contexts and links to harms. participants living with HCV from the opiate substation therapy. The proposed study involves analysis of Melbourne Injecting Cohort Study (SuperMIX). Interviews will address quantitative data collected through the The Networks 2 study was a longitudinal alcohol use and other related exposures Young Risky Drinkers (YRD) study. study investigating the social networks and outcomes, including participants’ of people who inject drugs. Participants The YRD is a representative sample of alcohol consumption prior to and after were asked about recent opiate 802 young high-risk drinkers recruited HCV diagnosis, any medical advice substitution therapy at each 3-monthly across metropolitan Melbourne regarding alcohol consumption they may interview and followed for three years. using Computer Assisted Telephone have received, advice from peers with Interviewing (CATI) during 2012. Specific HCV regarding alcohol consumption, In order to ascertain their social network, questions were asked about their most perception of alcohol consumption participants were asked who they inject recent episode of high-risk drinking. The practices amongst peers with HCV, drugs with, the nature of the social cohort was followed up in 2013 with a participants’ understanding of the connection (e.g., friendship, sexual similar questionnaire. Analysis will be relationship between alcohol-related and partners, kinship, etc). undertaken to characterise risky drinking injecting drug use-related behaviours, occasions and use findings from these clinical symptoms and other effects of This research study will investigate analyses at baseline to examine whether HCV on relationships and self-perception, the effect of the opiate substitution these predict subsequent experiences current self-management strategies for therapy status of the contacts on the of harm. Findings from the project will living with HCV. opiate substitution therapy usage of the present a unique picture of RSOD. individual. 19

2020 Projects Public Health

BEHAVIOURS AND HEALTH RISKS Inflammation as risk factor for Using simulation modelling to The potential of naloxone to reduce opioid overdose perform alcohol policy experiments opioid overdose deaths: modelling the impact of broader distribution Honours Honours, Masters by Research Honours, PhD Professor Paul Dietze Dr Nick Scott [email protected] [email protected] Dr Nick Scott Dr Philippe Boeuf Professor Paul Dietze [email protected] Professor Paul Dietze Professor Mark Stoové Acute harms experienced by young, Professor James Beeson heavy alcohol drinkers, such as verbal Globally, opioid overdose is on an aggression, being sick from drinking too increasing trajectory with as many as Opioid overdose is a significant public much or having difficulty getting home 60,000 US people dying every year in the health problem that has been increasing in after a night out are topics of significant USA. In Australia, around 1000 people recent years, with people who inject drugs public health concern. Although policies die from opioid overdose every year. particularly at risk of overdose. However, are often proposed to minimise these Fortunately, if an opioid overdose is a substantial percentage of those who harms, there is rarely any evidence attended in time it can be reversed with inject opioids do not experience overdose, available to support their effectiveness. naloxone, a drug that can be delivered suggestive of personal and biological risk However, computer-based simulation through an intra-muscular injection factors. models are effective, cutting-edge or an intranasal spray. To improve the research tools that are increasingly being timeliness of naloxone delivery to people Known risk factors include dose and route used to compare hypothetical policies, to experiencing overdose, take-home of opioid intake as well as concomitant help decide what is likely to be the most naloxone kits are now available that can use of alcohol or benzodiazepines. The effective and why this is the case. be carried by peers or family members biological bases for these associations of people at risk. To obtain a take-home are not known. However, some of these ‘SimDrink’ is an existing simulation naloxone kit, training on how to use it is risk factors could be linked with chronic model of a population of 18-25 year olds usually required. This can be provided by inflammation. engaging in heavy sessional drinking a range of community and professional on a night out in Melbourne. It has been groups such as outreach workers and For example, chronic alcohol purposely designed to provide a means pharmacists. Pilot studies have shown misuse is pro-inflammatory whereas for conducting alcohol policy experiments that peers are willing to use take-home benzodiazepines have anti-inflammatory to inform policy decisions. properties. This suggests that naloxone kits and that they are inflammation may be a central risk factor This project will gather data on current effective at saving lives. However, the for opioid overdose. Furthermore, chronic or proposed alcohol policies, develop/ population-level impact will depend on inflammation would also increase the risk program additional model features as how much coverage can be achieved of additional chronic disease and impact required, and compare the outcomes of among risk populations. on overall health. simulated individuals under different This project will use mathematical policy scenarios. Policy examples that modelling to estimate the potential Taking a unique biological approach to a could be tested include the effects of impact of take home naloxone kits if public health issue, we hypothesise that happy hours, changes to the enforcement they were distributed from a variety of inflammation is a major risk factor for of responsible service of alcohol, changes different sources, with different training/ opioid overdose with chronic inflammation to alcohol taxation, or gender based information requirements. Data from related to poor overall health. entrance policies for commercial venues. cohort studies and administrative Inflammatory markers will be quantified datasets will be analysed to obtain in plasma/serum samples collected from estimates of service utilisation, people who inject drugs. The student will ambulance callouts and opioid overdose be offered the opportunity to generate deaths to inform the model. The model these data if s/he wishes to do so. S/ will be used to assess the potential he will use biostatistical approaches coverage, cost and impact on mortality to control for known risk factors for of distributing take-home naloxone kits overdose to identify inflammatory markers through different sites and modalities, associated with opioid overdose as well as including pharmacies, opioid substitution potential causes of this inflammation. therapy clinics, specific needle and syringe programs, and prisons. This work This innovative project could lead will be used to inform the scale-up of to interventions aimed at reducing take-home naloxone in the community. inflammation in people who inject drugs in order to curb the rising rate of opioid overdose. 20

2020 Projects Public Health

Analyzing the impact of the North Evaluating health promotion Understanding ‘never overdosing’ Richmond supervised injecting strategies targeting alcohol and in a cohort of people who inject room using data from a cohort other drug use among the South opioids study of people who inject drugs Sudanese community in Melbourne Honours Honours Honours Ms Penny Hill [email protected] Dr Maria del Mar Quiroga Ms Carol El-Hayek [email protected] [email protected] Dr Peter Higgs Dr Peter Higgs Professor Paul Dietze Professor Paul Dietze Professor Paul Dietze Ms Caitlin Douglass Opioid overdose is a major public Professor Mark Stoové Evidence suggests that some culturally health problem globally, with overdose and linguistically diverse groups face incidence and mortality from overdose The Melbourne Injecting Drug User Cohort barriers to accessing information and increasing at rapid rates in North Study - SuperMIX is a cohort study of support for alcohol and other drug (AOD) America, with similar trends emerging in people who inject drugs (PWID) that has use. Barriers include shame and stigma, Australia. People who inject drugs (PWID) been running in various forms at the lack of culturally-specific services and are a key risk group for opioid overdose, Burnet Institute since 2008. It currently limited knowledge of available support. with rates of opioid overdose among contains a wealth of information related To address these barriers, Burnet Institute Australian PWID as high as 50 per cent. to injecting drug use behaviour for over and the Centre for Culture Ethnicity and But not all PWID experience overdose, 1200 individuals that have been Health will work with the South Sudanese despite long injecting careers and followed-up for different periods of time. community in Melbourne to deliver a high-risk environments. Harm reduction culturally-specific AOD program. The practices are encouraged in order to This project aims to examine the impact reduce the harm from non-fatal overdose of visiting the supervised injecting facility program will have multiple components including community education, and rates of fatal overdose, but evidence on the risk-related behaviours and service is limited on the self-acknowledged use of people who inject drugs. evaluation, bicultural workers and linkage of young people and families to treatment success of protective efforts that PWID This project is ideal for students in health services. utilise in order to protect themselves from sciences, psychology or quantitative overdose. disciplines (e.g computer science, The proposed honours project may include one or more of the following; This project aims to explore the mathematics, physics) who have a strong characteristics of PWID who have never interest in quantitative data analysis, and developing data collection tools, evaluating health literacy needs and overdosed, in comparison to PWID who using technology and data to make better have. evidence-based decisions in areas with conducting interviews with community clear social impact. members. This project would particularly suit a student who identifies as South Sudanese and has an interest in public health and health promotion.

FOR MORE INFORMATION GO TO burnet.edu.au 21

2020 Projects Public Health

BEHAVIOURS AND HEALTH RISKS Social networks of people who use drugs

Honours, Masters Dr Rachel Sacks-Davis [email protected] Professor Paul Dietze Dr Johan Koskinen (University of Melbourne)

Most behavioural and health risk research focuses on individual characteristics, ignoring the potential effects of social networks. For example, a typical study of overdose risk might investigate the role of age, gender, the type of drug used and drug use patterns, without considering the potential effect of social networks. However, social networks may be a key factor related to overdose related harms: for example, through norms related to risk behaviour which may differ by social group, or more directly through delivery of first aid or having someone to call emergency services.

Burnet Institute has collected data on the social networks of people who use drugs through several studies, including SuperMIX, the largest cohort of people who inject drugs ever conducted in Australia (there are currently more than 1200 participants), and VMAX, a cohort of 745 methamphetamine users. The objective of this project is to understand the characteristics of the social networks of the participants in these studies, and to investigate the influence of these characteristics on drug-related risk behaviours and harms, including cessation from and relapse into drug use, and overdose.

International Development International Development 23

2020 Project Summary International Development

Profiling the health needs of adolescents within the Are Australian guideline panels gender balanced? ...... 28 Asia and Pacific region ...... 24 Marketing of breast milk substitutes on breastfeeding Evaluating the use, impact and ongoing sustainability of practices in the Asia and Pacific region ...... 29 maternal and newborn health training programs in LMIC of immediate newborn care programs in the Asia and Pacific How baby friendly are Australian health services? WHO/ region ...... 24 UNICEF Baby Friendly Health Initiative (BFHI) accreditation efforts in Australia ...... 29 The state of abortion services in the Pacific ...... 24 How do we improve the knowledge and skills of midwives Improving sexual and reproductive health of adolescents in and doctors in assessment and classification of perineal Myanmar ...... 25 tears? ...... 29

Young people’s health and elimination of cervical cancer in Adolescent reproductive health status in developing Myanmar ...... 25 countries ...... 30

Immunisation programs in resource-constrained settings, Patterns of social determinants of access to maternal evidence collation for global policy ...... 25 health services in low- and middle-income countries .... 30

Infectious and nutritionalco-morbidities in pregnancy Public health strategies and tools to eliminate tuberculosis (TB) and health outcomes amongst women and newborns in in high-burden settings ...... 30 low- and middle-income countries ...... 26 Strengthening surveillance and response for resurgent or Global, regional, national estimates of induction of labour: resistant vector-borne pathogens in Papua New Guinea ..... 31 levels and trends ...... 26

What maternal health trials are conducted in low- and middle-income countries? ...... 26

Maternal sleep position and stillbirth prevention in low- and middle-income countries ...... 27

Trends in maternal and newborn health outcomes in Demographic Household Surveys in Papua New Guinea ... 27

Optimising the management of women in spontaneous preterm labour ...... 27

Understanding women’s values and preferences associated with calcium supplementation prior to and during pregnancy ...... 28

What is the prevalence of Rhesus alloimmunisation and associated poor outcomes among pregnant women in low and middle income countries? ...... 28

Please note: It is advised that all students include a copy of their most recent CV and official/unofficial academic transcript when contacting potential supervisors.

PROJECTS ARE COLOUR CODED TO THE APPROPRIATE PROGRAM:

Maternal and Disease Behaviours and Healthy Ageing Health Security Child Health Elimination Health Risks 24

2020 Projects International Development

MATERNAL AND CHILD HEALTH Profiling the health needs of Evaluating the use, impact and The state of abortion services in adolescents within the ongoing sustainability of maternal the Pacific Asia-Pacific region and newborn health training programs in LMIC of immediate Honours, Masters, MDRP, PhD Honours, Masters, PhD newborn care programs in the (1 year minimum preferred) Asia and Pacific region Dr Peter Azzopardi Professor Caroline Homer [email protected] Masters, MDRP [email protected] Dr Elissa Kennedy (min 1 year full time or Dr Alyce Wilson equivalent required) Dr Joshua Vogel The Asia-Pacific region (which includes 57 countries) is home to more than half of Professor Caroline Homer Dr Meghan Bohren the world’s adolescents. It is remarkably [email protected] (University of Melbourne) diverse, with countries at very different stages of epidemiological transition. Dr Joshua Vogel Abortion services are a key component Adolescents represent a large proportion Dr Michelle Scoullar of sexual and reproductive health of the population of this region, and services, yet access to safe, affordable represent significant opportunities for There are a number of maternal and and respectful abortion services are population health gain. However, the newborn health training programs now often limited especially in low- and health needs for adolescents in this being implemented across the world, middle-income countries. Worldwide, region are yet to be described. especially in low- and middle-income approximately 25 million unsafe countries (LMICs). These include abortions occur each year; the majority The aim of this project is to describe essential newborn care, emergency (97 per cent) of these occurring in low- national health profile(s) of adolescent obstetric and newborn care (EmONC), and middle-income countries. Restrictive health need in a country/countries of the the Helping Babies Breathe/Helping laws in these countries, coupled with Asia-Pacific region of particular interest Mothers Survive programs from Laerdal lack of available services and skilled and relevance. Relevant national and Global Health and Advanced Life providers, high cost of safe abortion regional stakeholders will be engaged, Support in Obstetrics (ALSO). It is not services and negative societal attitudes and a conceptual framework of health will known as the extent or penetration of towards abortion can contribute to high be defined. Data will then be sourced, these initiatives in different regions or rates of unsafe abortions. and may include data from the Global countries and the medium to long term Burden of Disease and/or available sustainability and impact. In this project, a student will examine country-specific primary data. the availability, access and affordability The Maternal and Child Health program of abortion services in the Pacific This data will then be used to describe a has a number of student projects region. Using the literature, the Global country profile identifying key needs for available relating to research on Abortion Policies Database and other adolescent health in that country (similar improving our understanding of the key databases, the student will perform to that defined in the Lancet Commission impact of emergency and in-service an analysis of current abortion services on Adolescent Health, figures 16 - 17). training in LMICs. in the Pacific region, identify gaps and Outputs will include manuscripts and highlight recommendations to prevent policy briefs. The student will work with the Global unintended pregnancies and unsafe Women’s and Newborn’s Health Group at abortions. The project will be developed Burnet Institute in Melbourne (primarily in collaboration with key researchers in desk-based research). This project will this area at UNSW, University of Sydney, allow the student to gain experience in PNG Institute for Medical Research, global maternal and perinatal health Family Planning NSW and University of epidemiology, systematic review and Melbourne. quantitative analysis methodologies, with a view to a scientific publication The student will work with the Global and pursuing a PhD. Women’s and Newborn’s Health Group at Burnet Institute in Melbourne (primarily desk-based research). This project will allow the student to gain experience in global maternal and perinatal health epidemiology, systematic review and quantitative analysis methodologies, with a view to a scientific publication.

25

2020 Projects International Development

MATERNAL AND CHILD HEALTH Improving sexual and reproductive Young people’s health and Immunisation programs in health of adolescents in Myanmar elimination of cervical cancer resource-constrained settings, in Myanmar evidence collation for global policy Honours, Masters Honours, Masters Honours, Masters Dr Elissa Kennedy [email protected] Dr Christopher Morgan Dr Christopher Morgan [email protected] [email protected] Dr Peter Azzopardi Dr Elissa Kennedy Adolescents aged 10-19 years account Childhood immunisation is the most for almost 20 per cent of Myanmar’s Elimination of cervical cancer in Myanmar cost-effective public health measure population and have high unmet and similar settings needs human available, yet approximately one in sexual and reproductive health papilloma virus (HPV) vaccination, five children are still not reached with (SRH) needs. Poor access to quality typically administered in schools, and vaccination, mainly in low- and information and services contribute to separate programs for screening women middle-income countries. Burnet Institute higher risk sexual behaviour, sexually for early signs. Our research aims to find staff have been working with the World transmitted infections, and early and ways to link these to find synergies that Health Organization (WHO) and Gavi, unintended pregnancy. Burnet is will maximise public health benefit and the Vaccine Alliance on prioritisation currently undertaking a 5-year project increase acceptability. of new devices or approaches to to improve the quality of school-based immunisation programs. To support comprehensive sexuality education Aims: this, there are several specific topics for (CSE), improve the delivery of adolescent- 1) To review evidence, relevant to which up-to-date collation of evidence is friendly health services (AFHS), and low- and middle-income settings, on needed, including evidence on common increase community support for young active linkages between HPV vaccination programmatic errors, or vaccination by people in communities in Magway and and school health with cervical cancer lesser-trained personnel. Tanintharyi Regions, Myanmar. screening services Aims: The aim of this project is to describe 2) To analyse data on feasibility and a) To support the collation and analysis SRH knowledge and attitudes among acceptability of linked vaccination and of evidence from resource-constrained adolescents, teachers and health screening in Myanmar. settings to support global strategies for providers and explore barriers to innovative immunisation programs providing quality CSE and AFHS. This Methods: b) To generate evidence from specific project could include a) analysis of 1) Scoping review of published literature settings in Africa, Asia or the Pacific to quantitative data to describe SRH guide local policy or procedures. knowledge and attitudes of adolescents, 2) qualitative data analysis of interview and discussion data collected by the teachers and health providers and Methods: satisfaction with / confidence delivering Burnet Myanmar field team. The latter will Research activities can include: a) review CSE and AFHS; b) analysis of qualitative cover topics including HPV vaccination of country-level data and publications to data to explore in-depth barriers to of girls, adolescent health promotion inform WHO technical advisory groups; providing CSE and AFHS; or c) evaluation priorities, and use of new technologies and/or b) a systematic or scoping of a community-based intervention to for cervical cancer screening in women. literature review. Students will gain a improve parents’ communication about Students will gain skills in health detailed insight into global health policy SRH. Outputs will include manuscripts systems thinking and implementation development, and the application of and policy briefs. research, as used to generate evidence evidence to inform health policy, as useful for global public health policy it applies to the global vaccination and practice, oriented to low- and program. Students will also gain skills middle-income settings. Technical in systems thinking, health systems knowledge areas encompass adolescent analysis, systematic literature reviews, health, vaccination programs, and and the collation and presentation of women’s reproductive health. Students evidence to inform policy. will also gain skills in systems thinking, health systems analysis, systematic Outputs: literature reviews, and the collation and Evidence review publication, research presentation of evidence to inform policy. design, research report, policy briefs. Outputs: Evidence review publication, qualitative data analysis report, policy briefs. 26

2020 Projects International Development

Infectious and nutritional Global, regional, national What maternal health trials co-morbidities in pregnancy and estimates of induction of labour: are conducted in low- and health outcomes amongst women levels and trends middle-income countries? and newborns in low- and middle-income countries Masters, PhD Masters, PhD PhD preferred (minimum 1 year (minimum 1 year full-time or Honours, Masters, MDRP, PhD full-time or equivalent required) equivalent required, PhD preferred) (1 year minimum preferred) Dr Joshua Vogel Dr Joshua Vogel Dr Michelle Scoullar [email protected] [email protected] [email protected] Professor Caroline Homer Professor Caroline Homer Professor Caroline Homer Dr Tari Turner Dr Joshua Vogel Dr Alyce Wilson Well-performed randomised controlled Dr Alyce Wilson Induction of labour is a common practice trials are a robust design that can be used Despite substantial efforts, globally over for women in high-income countries— to evaluate the benefits and harms of the 300,000 women die each year during accounting for nearly a third of all effects of different interventions. They pregnancy, childbirth, or the postpartum births in Australia. While there are less can also be used to in implementation period, mostly from preventable causes. population-based data on the use of research contexts to determine the most Although this burden disproportionately labour induction in low- and middle- effective strategies for improving the occurs in communities in low- and income countries (LMICs), some large use of interventions. While the volume middle-income countries (LMICs), it also observational studies have shown of maternal health research published affects increasing numbers of women induction rates similar to those of high- increases every year, there has not yet in disadvantaged communities in some income countries. There is also evidence been a review of where and on what high-income countries. It has been to suggest induction use is rapidly maternal health conditions these trials recognised that indirect causes (such increasing in some LMICs. Over-use or are conducted, and whether the research as non-communicable diseases and inappropriate use of labour induction is conducted aligns the burden of maternal malnutrition) are playing an increasingly probably contributing to rising rates of health morbidity and mortality in these significant role in the global burden. caesarean section, avoidable maternal countries. and fetal harm and unnecessary health Many women in LMICs experience expenditure. Currently there are no In this project, a student will conduct multiple co-morbidities simultaneously estimates at global or regional levels a systematic review of published trials – for example, having anaemia, malaria (or for many LMICs) on the use of labour on maternal health topics conducted and sexually transmitted infections induction, though similar estimates exist in low- and middle-income countries. concurrently. Emerging evidence suggests for caesarean section. The student will work with the Global that when these conditions overlap, Women’s and Newborn’s Health Group the negative effects may be synergistic In this project, a student will conduct a at Burnet Institute in Melbourne rather than additive. This project will systematic review of available data on (primarily desk-based research). involve a systematic review to examine use of labour induction to assess levels This project will allow the student to the association of co-morbidities during and trends in induction use worldwide. gain experience in global maternal and pregnancy and their effect on maternal Depending on data availability, methods perinatal health epidemiology, systematic and newborn health outcomes in LMICs. of labour induction, effects on health outcomes and expenditure could also be review and quantitative analysis The student will work with the Global explored. methodologies, with a view to a Women’s and Newborn’s Health Group at scientific publication. Burnet Institute in Melbourne (primarily The student will work with the Global desk-based research). This project will Women’s and Newborn’s Health Group at allow the student to gain experience in Burnet Institute in Melbourne (primarily global maternal and perinatal health desk-based research). This project will epidemiology, systematic review and allow the student to gain experience in quantitative analysis methodologies, global maternal and perinatal health with a view to a scientific publication and epidemiology, systematic review and pursuing a PhD. quantitative analysis methodologies, with a view to a scientific publication. 27

2020 Projects International Development

MATERNAL AND CHILD HEALTH Maternal sleep position and Trends in maternal and newborn Optimising the management of stillbirth prevention in low- and health outcomes in Demographic women in spontaneous preterm middle-income countries Household Surveys in Papua New labour Guinea (2006 and 2018) Honours, Masters, MDRP, PhD PhD, Masters, MDRP (1 year minimum preferred) Honours, Masters, MDRP Dr Joshua Vogel Dr Joshua Vogel Dr Joshua Vogel [email protected] [email protected] [email protected] Dr Michelle Scoullar Professsor Caroline Homer Professor Caroline Homer Professor Caroline Homer Stillbirth is a major cause of mortality Dr Alyce Wilson Preterm birth affects nearly 15 million globally, with an estimated 2.6 million Dr Meghan Bohren births annually, and is the leading cases worldwide in 2015 and over 150,000 (University of Melbourne) cause of death in children younger than in the South-East Asia and Oceania region five years of age globally. Up to 75 per alone. Approximately 98 per cent of these Demographic and Health Surveys (DHS) cent of preterm births occur following stillbirths occurred in low- and middle- are large, nationally-representative spontaneous preterm labour or preterm income countries, and half (1.3 million) household surveys that provide data for premature rupture of membranes during labour and birth (intrapartum). These a wide range of monitoring and impact (PPROM). In Australia, preterm birth affects numbers are staggering on their own, and evaluation indicators across population, 8.5 per cent of all births (an increase from even more so when taking into account the health, and nutrition topics. In many 7.9 per cent in 2010), equating to nearly grief experienced by millions of families, most low- and middle-income countries (such 27,000 preterm babies in 2016. of whom need not have suffered this highly as Papua New Guinea), the lack of national civil administrative data means preventable outcome. With strategies for preventing preterm that governments, international agencies birth proving largely unsuccessful, women Recent observational studies have linked and funders rely on DHS data for many presenting with signs and symptoms of maternal sleep position (supine) to an reproductive health indicators. threatened preterm labour remains a increased risk of stillbirth. Australian global clinical challenge. Tocolytic drugs healthcare providers are encouraged to In Papua New Guinea, a new DHS (data are widely used in an attempt to delay or provide all pregnant women with safe collected 2017-2018) will be released in even prevent preterm birth. In Australia, sleeping advice (in addition to other late 2019, superseding the previous DHS the calcium channel blocker nifedipine is interventions) to help prevent stillbirths 2006. The availability of these new data routinely used to treat threatened preterm from occurring. However, there is limited provide a unique opportunity to assess labour. However, a Cochrane review information as to whether sleep position is a trends in key maternal and newborn found insufficient evidence to conclude risk factor for stillbirth in low-resource, high- health indicators in PNG over the whether tocolysis with nifedipine improves burden countries, where stillbirth rates are past decade. substantive perinatal outcomes. substantively greater than Australia. In this project, a student will conduct Projects available: a comparative analysis of the two The Maternal and Child Health Program has a number of student projects available 1. Systematic review of observational Demographic Health Surveys (2006 relating to research on improving studies reporting maternal sleeping and 2018) available for Papua understanding and use of nifedipine behaviour during pregnancy New Guinea, to assess trends in socio-demographic characteristics, for the management of preterm labour, 2. Primary research on the perspectives reproductive health service utilisation including: and beliefs of women and providers in and maternal and newborn health • Knowledge synthesis on the benefits LMICs around sleeping practices and risk outcomes. The student will work with the and harms of nifedipine for preterm of stillbirth Global Women’s and Newborn’s Health labour, including systematic reviews 3. Primary observational research on Group at Burnet’s in Melbourne (primarily of efficacy trials women’s sleep position and health desk-based research). This project will • Reviews and quality assessments of outcomes in LMICs, using wearable allow the student to gain experience in relevant international clinical technologies global maternal and perinatal practice guidelines The student will work with the Global health epidemiology with view to • Primary research on current clinical Women’s and Newborn’s Health Group at a scientific publication. practice in managing spontaneous the Burnet Institute in Melbourne (primarily preterm labour, including desk-based research). This project will allow tocolytic use the student to gain experience in global maternal and perinatal health epidemiology, • Primary research on women’s and systematic review and quantitative analysis provider’s willingness to participate methodologies, with a view to a scientific in a clinical trial of nifedipine versus publication and pursuing a PhD. placebo. 28

2020 Projects International Development

Understanding women’s values What is the prevalence of Rhesus Are Australian guideline panels and preferences associated with alloimmunisation and associated gender balanced? calcium supplementation prior to poor outcomes among pregnant and during pregnancy women in low and middle income Masters, MDRP, PhD countries? Masters, MDRP, PhD Dr Joshua Vogel (minimum 1 year full time or Masters, MDRP, PhD [email protected] equivalent required) (minimum 1 year full time or Dr Meghan Bohren equivalent required) (University of Melbourne) Dr Joshua Vogel [email protected] Dr Joshua Vogel Professor Caroline Homer [email protected] Dr Alyce Wilson Dr Meghan Bohren (University of Melbourne) Dr Michelle Scoullar The development of clinical guidelines is Globally, many women do not receive In pregnancy, Rhesus (Rh) negative an important leadership role in clinical a sufficient amount of calcium during mothers can develop Rh antibodies medicine and public health. Guideline pregnancy, particularly in low -and if they have an Rh-positive newborn. panels are typically composed of leading middle-income countries where dietary This can cause haemolytic disease technical experts in a particular field, as calcium intake is low. World Health of the newborn in subsequent well as representatives of key stakeholder Organization recommends that in pregnancies. Consequently, in 2016, groups such as professional associations, populations with low dietary calcium WHO recommended that administering consumer representatives and guideline intake, pregnant women take daily anti-D immunoglobulin to Rh- negative implementers. An analysis of the calcium supplementation to reduce women within 72 hours of giving birth to gender composition of 230 World Health the risk of pre-eclampsia. A recent an Rh-positive baby is an effective way Organisation guideline panels in the past trial has demonstrated that there of preventing RhD alloimmunisation and eleven years showed that more panel may also be some benefits in calcium newborn morbidity. members were male, and two-thirds of supplementation prior to pregnancy guideline panels had a male Chair. for women who have experienced The 2016 guideline panel also identified In this project, a student will conduct pre-eclampsia in a previous pregnancy. that determining the prevalence of RhD alloimmunisation and associated poor an analysis of the gender composition However, high-dose calcium outcomes among women in low- and of Australian guideline panels over the supplementation is unpalatable to middle-income country (LMIC) settings past ten years. It will involve developing many women, as tablets can be large, is a research priority. Understanding the a database of guideline panel members have a powdery texture, and require prevalence of RhD alloimmunisation using the NHMRC guideline clearinghouse taking three tablets a day (in addition to in different LMICs allows health website, and conducting a descriptive other supplements). These factors have decision-makers to prioritise the quantitative analysis. implications for women’s acceptability of implementation of anti-D immunoglobulin The student will work with the Global calcium supplementation, and can inhibit programmes within the context of Women’s and Newborn’s Health Group at the success of programs to promote good improving the quality of maternal and Burnet Institute in Melbourne (primarily nutrition in pregnancy. newborn healthcare. desk-based research). This project would In this project, a student will conduct a In this project, a student will conduct a allow a student to gain experience in systematic review aimed at identifying systematic review aimed at identifying gender theory and quantitative analysis available qualitative evidence on available evidence on the prevalence of methods, with a view to a scientific women’s perspectives and experiences Rh alloimmunisation amongst women publication. The findings will be around calcium supplementation during giving birth in low- and middle-income critical for Australian healthcare pregnancy. The student will work with the countries. The student will work with the decision-makers. Global Women’s and Newborn’s Health Global Women’s and Newborn’s Health Group at Burnet Institute in Melbourne Group at Burnet Institute in Melbourne (primarily desk-based research). This (primarily desk-based research). The project will allow the student to gain project will allow the student to gain experience in global maternal and experience in global maternal and perinatal health, systematic review perinatal health and systematic methodologies, with view to a review methodologies, with view to scientific publication. a scientific publication. 29

2020 Projects International Development

MATERNAL AND CHILD HEALTH Marketing of breast milk How Baby Friendly are Australian How do we improve the knowledge substitutes on breastfeeding health services? WHO/UNICEF Baby and skills of midwives and doctors practices in the Asia-Pacific Friendly Health Initiative (BFHI) in assessment and classification of accreditation efforts in Australia perineal tears? Honours, Masters, MDRP, PhD (1 year minimum preferred) Honours, Masters, MDRP, PhD Honours, Masters, MDRP, PhD (1 year minimum preferred) (1 year minimum preferred) Dr Alyce Wilson [email protected] Alyce Wilson Dr Alyce Wilson [email protected] [email protected] Professor Caroline Homer Professor Caroline Homer Professor Caroline Homer Dr Joshua Vogel Dr Meghan Bohren Dr Joshua Vogel Dr Meghan Bohren (University of Melbourne) (University of Melbourne) Dr Meghan Bohren (University of Melbourne) Dr Joshua Vogel The infant formula industry is worth Severe perineal tears (third- and US$70 billion a year and growing. The World Health Organisation/UNICEF fourth-degree tears) are associated Despite sales stagnating in high income Baby Friendly Health Initiative (BFHI) was with significant immediate and long countries, infant formula sales continue launched in 1991 with the global goal of term implications for women and health to grow in low- and middle-income encouraging health services to protect, systems. In Australia, rates of third- and countries. The World Health Organization promote and support breastfeeding fourth-degree tears are above rates recommends that all babies initiate of singleton and multiple births. for similar OECD countries and there is breastfeeding within the first hour of Since its inception, the BFHI has been significant variation across states and birth, feed exclusively on breast milk implemented in more than 152 countries territories. Many maternity services for the first six months and continue worldwide, including in Australia in across Australia are driving their own to breastfeed for up to two years and 1993. Health services can apply for initiatives to reduce the incidence of beyond. Moreover, breastfeeding is BFHI accreditation to demonstrate severe perineal tears and this is further recognised as a key newborn and child their commitment to providing a supported by state and national efforts survival intervention and it is estimated supportive environment and service for to establish best practice guidelines and that if all babies were exclusively breastfeeding. In 2012, Australian Health clinical standards. breastfed to six months of age, 823,000 Ministers encouraged both public and deaths in children under five years could private hospitals to achieve and maintain It has been recognised that improving be saved each year. BFHI accreditation, and affirmed that all the competency of midwives and state and territory health services should doctors in assessing and accurately The infant formula industry is increasingly implement the (BFHI) particularly the ten classifying perineal tears could be one targeting low- and middle-income steps to successful breastfeeding for all avenue through which to achieve better countries in their marketing efforts, health services. prevention and management of severe especially in the Asia-Pacific region. perineal tears. This project will involve a The pervasive marketing of the formula This project will involve mapping BFHI systematic review to examine initiatives industry plays a key role in lagging accredited facilities in Australia and undertaken to educate and train midwives breastfeeding rates and can contribute to comparing efforts between states and and doctors in perineal anatomy and suboptimal infant feeding practices. This territories and impact on breastfeeding classification of perineal tears. project will involve a systematic review rates. Surveys will be undertaken with to examine the influence of the infant health facilities that are yet to achieve The student will work with the Global formula industry on breastfeeding rates in accreditation to explore perceived Women’s and Newborn’s Health Group the Asia Pacific region. enablers and barriers to at the Burnet Institute in Melbourne BFHI accreditation. (primarily desk-based research). This The student will work with the Global project will allow the student to gain Women’s and Newborn’s Health Group at The student will work with the Global experience in global maternal and Burnet Institute in Melbourne (primarily Women’s and Newborn’s Health Group at perinatal health epidemiology, systematic desk-based research). This project will Burnet Institute in Melbourne (primarily review and quantitative analysis allow the student to gain experience in desk-based research). This project will methodologies, with a view to a scientific global maternal and perinatal health allow the student to gain experience in publication and pursuing a PhD. epidemiology, systematic review and global maternal and perinatal health quantitative analysis methodologies, with epidemiology, systematic review and a view to a scientific publication. quantitative analysis methodologies, with a view to a scientific publication and pursuing a PhD. 30

2020 Projects International Development

HEALTH SECURITY Adolescent reproductive health Patterns of social determinants of Public health strategies and tools status in developing countries access to maternal health services to eliminate tuberculosis (TB) in in low- and middle-income countries high-burden settings Honours, Masters Honours, Masters Honours, Masters Dr Mulu Woldegiorgis [email protected] Dr Mulu Woldegiorgis Dr Philipp du Cros [email protected] [email protected] Professor Mark Stoové Professor Mark Stoové Dr Suman Majumdar Adolescence is a critical time of transition Professor Steve Graham from childhood to adulthood with a Reducing maternal mortality is one of the major goals of health systems in low- and marked biological and social change. Tuberculosis is treatable and curable. middle-income countries, having been Every year, about 20 per cent However, due to political, financial and included as one of the eight Millennium of adolescents give birth in low- and scientific neglect, tuberculosis remains Development Goals and retained as a middle-income countries. Poorer a global public health crisis, with an priority in the subsequent Sustainable maternal, child and broader social estimated 1.6 million people dying Development Goals. Maternal deaths outcomes are typically observed in annually. In 2015, the World Health mostly occur during labour, delivery relation to adolescent motherhood. In Organization (WHO) launched the End TB and early postnatal period. To address low- and middle-income countries, this Strategy, a package of interventions that this challenge, there have been several is often a consequence of early and/or fall under three pillars: patient-centred international and national initiatives arranged marriage, unprotected sex and care; supportive systems; and intensified aimed at reducing maternal mortality. limited access to other contraception research. There remains a significant Despite some progress, more than options that lead to unintended gap between the END-TB strategy targets 830 mothers still die every day from pregnancy, exposure to sexually and implementation on the ground. The preventable causes. Access to quality transmitted infections and mental health ambitious goal of ending tuberculosis maternal health services can avert these problems. Pregnancy and childbirth will not be realised without new models preventable maternal deaths. However, complications are the main causes of of service delivery and novel diagnostics, most mothers in low and middle-income death among pregnant adolescents. treatments and vaccine. Targeted interventions such as increasing countries do not receive quality maternal age at first marriage, increasing access to health services. Aims: contraception, reducing unsafe abortion Social determinants are important 1) What have been the approaches, and increasing access to famly planning factors influencing access to quality enablers and barriers to past attempts and maternal health services are maternal health services. However, there to eliminate infectious diseases (e.g. suggested priority interventions. is limited evidence about the pattern of smallpox, malaria, guinea-worm disease)? Using periodic data on family planning, influence between these determinants a)Review strategies for disease elimination maternal health and other relevant and maternal health service access and in resource vs limited settings using a programs from the Demographic Health health outcomes. This project aims to structured framework Survey, the aim of this project is to assess trajectories of social determinants b) Review historical TB control strategies in determine variations in patterns of of access to maternal health services and Australia and Papua New Guinea their impact on maternal health service adolescent pregnancy, motherhood and 2) Assess current TB policies in high- coverage in low and middle-income contraceptive use in low- and middle- burden countries in the Asia-Pacific region income countries and assess country, countries. The student will have access to Demographic and Health Surveys (DHS) systems and individual-level factors Methods: This work applies health data and world development indicators associated with these outcomes. systems thinking and implementation of low- and middle-income countries. research tools to the extraction of evidence DHS data is collected from nationally on service delivery from published and representative household survey grey literature. Research activities can participants and includes geolocated include: a) review of country-level data data in the areas of population and publications to inform WHO technical characteristics, health, and nutrition. advisory groups; and/or b) systematic DHS data are collected via literature review. Students will gain skills face-to-face interviews using in health systems analysis, systematic standardised questionnaires. World literature reviews, and the collation and development indicator data can be presentation of evidence to inform policy. obtained from the United Nations and other international agencies. Outputs: Evidence review publication, research design, research report, policy briefs. 31

HEALTH SECURITY Strengthening surveillance and response for resurgent or resistant vector-borne pathogens in Papua New Guinea Honours, Masters, PhD Associate Professor Leanne Robinson [email protected]

Emerging infectious diseases pose an intensifying global health threat, especially in the context of fragile health systems in developing countries. A pressing need therefore exists for continued surveillance, rapid diagnosis and real-time tracking of emerging infectious diseases and antimicrobial resistance.

In Papua New Guinea (PNG), Japanese Encephalitis (JEV), Murray Valley Encephalitis (MVEV) and West Nile/ Kunjin viruses have been detected and are likely to be endemic, although data is limited. In addition, despite impressive reductions in the incidence of malaria in the region in recent years, threats of spreading drug- and insecticide- resistance exist and there has been a resurgence of malaria in coastal areas of PNG. This is of major concern given the porous nature of borders between Indonesia, PNG and Australia, where cross-border travel is rapidly increasing and the opportunities for the next emerging infectious disease to be imported and spread throughout the region are ripe.

STRIVE PNG aims to generate evidence to enable the implementation of rapid -response strategies for surveillance of malaria and other VBDs in PNG and assess the feasibility, acceptability and financing of new policy options for stronger national surveillance and systems support. 32

Notes For more information: burnet.edu.au/education_and_training [email protected]

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