Mana Tangata I People Leadership: Te Niwha Priority Area

JESSICA LEONG 
University of Otago

Whakarāpopoto Rangahau I Summary of Research

Inherent antiviral host factors play a critical role in defence against human pathogens, including influenza A virus (IAV). Host histone deacetylase 2 (HDAC2) has been discovered to inhibit IAV infection. HDAC2 regulates the IAV induced host innate immune response, however, HDAC2 involvement in the regulation of specific innate genes remains unsolved. This project aimed to elucidate the role of HDAC2 during IAV-induced host innate immune response. The study involved overexpressing HDAC2 in human lung epithelial cells, infecting them with IAV and analysing the innate genes over 24 hours of infection using molecular methods.

Research Findings

The influenza virus is the cause of a contagious human respiratory disease commonly known as the ‘flu’. Influenza viruses cause occasional pandemics and recurring seasonal epidemics, which are a top contributor to our current healthcare burdens every winter. Vaccine efficacy against influenza viruses vary annually and rising drug resistance amongst the different strains call for alternative anti-influenza strategies. This requires uncovering the intricate networks within the human defense system during influenza virus infection. 

The Husain lab has discovered a family of human antiviral proteins called host histone deacetylases (HDACs); the antiviral mechanism of these HDACs is not yet fully understood. The student hypothesized that HDAC2, a member of the HDAC family, is involved in the host defense mechanisms against influenza A virus (IAV). In this project, the expression of the HDAC2 gene was manipulated in human lung cells and then the host innate immune response was measured in response to IAV infection. The results showed manipulation of HDAC2 caused significant changes in the expression of host innate immune response genes during IAV infection. This suggests that HDAC proteins could be directly involved in regulating the expression of innate immune response genes during IAV infection. The findings from this project provide insights into the complex immune pathways which may be regulated by HDACs during IAV infection and a basis for further research in infectious diseases.

ELIZABETHER CHERNYSHEVA 
University of Otago

Whakarāpopoto Rangahau I Summary of Research 

Legionella bacteria are a major cause of hospital admissions for community-transmitted pneumonia in New Zealand. Proper management and treatment depends on rapid identification of the pathogen causing the infection. However, current testing methodologies rely on collection of sputum samples from severely ill (and often intubated) patients. The goal of this project was to develop a highly sensitive diagnostic assay that can detect trace amounts of bacterial DNA circulating in the bloodstream, allowing a less invasive diagnosis and treatment of Legionnaires’ disease. This will also provide a diagnostic platform for other infectious diseases where sample collection is challenging.

Research Findings

Legionnaires’ disease is a type of pneumonia caused by Legionella bacteria which, if left untreated, may result in death. A crucial part of successful management of this illness is an early diagnosis and prescription of appropriate antibiotic medication. However, the symptoms of Legionnaires’ disease are almost identical to other types of pneumonia, and testing for the disease is not a routine procedure. This is partially because the sample needed for testing is difficult to obtain, and the procedure can be very stressful for patients. The result is that broad scope antibiotics are prescribed to most patients who present with pneumonia symptoms, which feeds directly into the global issue of antibiotic resistance. The aim of this project was to design a test that is able to diagnose Legionnaires’ disease using a blood sample, which is a routine procedure in most clinical practices around the world and causes little to no stress to the patient. Over the course of the Summer Studentship the research team was able to design and optimise a diagnostic method based on CRISPR-Cas technology. The next step in the process will be to validate these methods using clinical blood samples. The success of this project could eventually provide hospitals and clinics around New Zealand with a tool for the fast and sensitive diagnosis of Legionnaires’ disease, which will lead to better patient outcomes. 

DOUGLAS YEE 
University of Otago

Whakarāpopoto Rangahau I Summary of Research 

This research project used Stats NZ’s Integrated Data Infrastructure (IDI) to examine the uptake of school-age vaccinations (age 11/12 Tdap and HPV). It examined uptake over time, with the focus on the impact of COVID-19 restrictions and to what extent uptake may have caught up afterwards. The detailed level of linked data available in the IDI, which includes National Immunisation Register data as well as information from numerous other sources will allow for the examination of personal, family and school characteristics.

Research Findings

The COVID-19 pandemic caused widespread population health impacts. Following government mandated school closures, vaccinations usually administered through schools were delayed or put off entirely. There were also concerns the COVID-19 policy response could cause further ethnic disparities in immunisation uptake.

The student used data from Stats NZ’s Integrated Data Infrastructure (IDI) to examine the uptake of school-aged vaccinations (Tdap and HPV) among 10.5 – 14 year olds by ethnicity, with specific focus on three time points: (1) a policy change extending the HPV vaccine rollout to include males and females aged 9-26, (2) the initial COVID-19 lockdown in March 2020, and (3) a significant COVID-19 lockdown in August 2021.

Initial results show even prior to COVID-19, vaccination rates were well below target and falling. However, there doesn’t appear to be a substantial COVID-19 effect when looking at vaccination trends alone. Where there does seem to be a COVID-19 effect, vaccination uptake subsequently improves, indicating catch-up. There does appear to be emerging ethnic disparities that do not favour Māori and Pasifika, who were initially highly vaccinated relative to Europeans and Asians, but are less vaccinated post-2017 and post-COVID.

Findings to date on this project consist of preliminary results suggestive of socio-economic disparities in vaccination uptake, while future iterations of the research will consider other factors that may drive these disparities in more detail. Understanding characteristics that influence healthcare utilisation has the potential to inform policies that promote equitable access to healthcare services. 

GEORGIE ALLEN 
University of Otago

Whakarāpopoto Rangahau I Summary of Research 

LARISSA RENFREW 
Hapai te Hauora

Whakarāpopoto Rangahau I Summary of Research 

Respiratory tract infections are a leading cause of morbidity and mortality in Aotearoa New Zealand, with influenza and respiratory syncytial virus (RSV) identified as key contributors. Māori can be particularly vulnerable to influenza and other respiratory infections. This project expanded on hospital-based surveillance of pre-school children through kohanga reo to support the understanding of the influenza and other respiratory virus disease burdens for children in a community setting and provide a more complete picture of the overall disease burden. Understanding patterns of transmission (particularly of influenza and RSV) among kohanga reo could guide an approach or strategy to reduce the high burden of RSV for Māori communities.

Research findings

As COVID-19 restrictions were gradually reduced and the Aotearoa New Zealand border opened leading to increasing international travel, an increase in respiratory viral infections was expected. Specifically, cases of RSV and cases of influenza, neither of which were detected in New Zealand during the past winter.

Project aims were to:

·      establish respiratory surveillance in Māori communities

·      understand the role of respiratory viruses including influenza and respiratory syncytial virus (RSV) in Māori aged 0-5 years old who attend kohanga reo with acute respiratory symptoms

·      estimate the presence of respiratory viruses in Māori children aged 0-5 years old who attend kohanga reo who are asymptomatic

·      explore the experiences of whānau Māori with children aged 0-5 years old who attend kohanga reo and are impacted by respiratory viral infections.

Community surveillance was undertaken at several kohanga reo and 70 whānau were recruited to the swabbing component of the project. The student was given training around data collection, collection of nasal swabs, as well as privacy and confidentiality and worked with their supervisor and wider research team to maintain whanaungatanga with kohanga reo, and collect data for the project through nasal swabbing and qualitative whānau interviews. At the end of the project, the student will provide a report and analysis of the whānau interviews, as well as a reflexive analysis on the process of data collection within Māori communities and the importance of Māori research principles within community level research.

JINWEI SUN 
University of Auckland

Whakarāpopoto Rangahau I Summary of Research

Antimicrobial resistance (AMR) is one of the most serious global health issues affecting the effective treatment of bacteria, parasites, viruses, and fungi. The issue of AMR is especially pressing in bacterial resistance which kills at least 700,0000 people globally each year and is predicted to outstrip mortalities from cancer, diabetes and AIDS by 2050. In Aotearoa New Zealand, AMR significantly disproportionately affects Māori because of increased vulnerability to pathogenic organisms and antibiotic dependency. Peptides are promising alternatives as antibacterials as they act by specific mechanisms of action making it difficult for bacteria to establish resistance. Daptomycin is a marketed lipidated peptide and is effective in treating bacterial infections caused by antibiotic-resistant Gram positive bacteria. However, the increased use of Daptomycin has led to the emergence of resistant strains. It is important to develop new Daptomycin-based antibiotics to mitigate AMR. This research aimed to develop new antibiotics by exploring the functionality of one of the key amino acid residues in daptomycin which is essential for its antibacterial activity.

Research findings

Daptomycin was the first antibiotic in its class to be developed in more than 40 years, and it was FDA-approved in 2003 for serious Gram-positive bacterial infections, but it is only used as a last-line-of-defence drug. The increased use of the antibiotic Daptomycin has led to the emergence of resistant strains. Several reports of S. aureus daptomycin resistance, as well as resistance in other Gram-positive bacteria such Enterococci, E. faecalis, S. aureus, and E. faecium, show the need for new Daptomycin-based antibiotics. Therefore, it is essential to develop Daptomycin-based antibiotics to overcome antimicrobial resistance. In this study, the viability of the modification of Kynurenine, a key amino acid in Daptomycin has been examined by using acetophenone and 2-aminoacetophenone, as they both have similar structures as Kynurenine. The aim was to install different chemical groups on the aromatic ring of Kynurenine, using a C-H insertion reaction. Acetophenone could be successfully functionalised but using 2-aminoacetophenone that more closely resembles the Kynurenine was unsuccessful, probably due to the presence of the amino group. Therefore, various methods were investigated to mask the reactivity of the amino group before carrying out C-H insertion and although protecting groups could be installed on the amino group, the subsequent C-H functionalization did not proceed. The research team anticipates that if the correct protecting group for the amino group is found it will result in the development of a new class of Daptomycin antibiotics for the treatment of Gram-positive bacterial infections.

SOPHIA HAMADA 
University of Auckland

Whakarāpopoto Rangahau I Summary of Research

Osteomyelitis is a disease causing inflammation of the bone and is predominantly due to infections caused by Staphylococcus aureus. Despite being rare, the disease has become a significant issue amongst paediatrics in Aotearoa New Zealand. Flucloxacillin is currently being used as a first-line treatment, though with the tolerance to antibiotics seen for S. aureus biofilms, some infections have been more difficult to treat. The aim of this research was to determine key bacterial gene markers involved in S. aureus antibiotic resistance by performing phylogenetic and genome analyses between osteomyelitis isolates having been cleared of infections compared to the more complicated cases.

Research findings

Acute haematogenous osteomyelitis (AHO) is a blood-borne infection where bacteria in the bloodstream attach to injured bone. Eventually, the bone becomes inflamed, further leading to bone loss and destruction. AHO is a significant issue among the paediatric population in New Zealand and is often caused by Staphylococcus aureus bacteria. Although most infections can be treated with antibiotics alone, some cases have been more challenging to treat. This may be the result of specific genes possessed by S. aureus that contribute to antibiotic resistance and pathogenicity. This project analysed the genes present in 94 S. aureus AHO bacteria (taken from patients from Starship Children’s Hospital between 1997 and 2007 and Middlemore’s Kidz First Hospital between 1998 and 2008 in Auckland, New Zealand) and explored whether there is a relationship between the S. aureus bacteria in patients that were easily treated with antibiotics compared to the more complicated ones.

From beginning with raw sequences, the student produced 94 assembled S. aureus genomes, a basic phylogenetic tree and a custom-created biofilm gene database. These results will be used as a starting point for the student’s Masters degree. By having assembled genomes, she can screen the genomes for antibiotic resistance, virulence factor genes and biofilm formation genes. As the project progresses in the future, with further genomic and phylogenetic analyses being completed, the team can correlate this data with phenotypic and clinical data collected by others in the wider research group. Together this will further understanding of antibiotic resistance in PAHO infections and help continue successfully treating PAHO.

SOPHIA HAMADA 
University of Auckland

Whakarāpopoto Rangahau I Summary of Research

New solutions to combat multi-drug resistant (MDR) bacteria are desperately needed to avert a looming public health crisis. Polymyxins are a last line of defence therapy for Gram-negative infections, however, their clinical effectiveness and utility is significantly limited by severe nephrotoxicity (or toxicity in the kidneys), occurring in up to 60% of patients. By modifying key hydrophobic motifs of the polymyxin chemical structure, the Brimble laboratory is currently developing novel polymyxin analogues with maintained antimicrobial potency (towards planktonic bacteria) and dramatically (approx. 10-fold) reduced toxicity. However, diseases associated with Gram-negative biofilms are notoriously recalcitrant, making anti-biofilm activity an essential development goal for novel antimicrobials. This project aimed to prepare novel polymyxin analogues to evaluate their anti-biofilm efficacy in collaboration with Richard Douglas (FMHS, University of Auckland).

Research findings

The phenomenon of antimicrobial resistance (AMR) has globally and rapidly progressed. With the discovery of novel antibiotics slowing down a long-abandoned lipopeptide-based antibiotic, polymyxin B (PMB), was re-evaluated as it could potentially breach the antibiotic-resistant envelope of bacteria, but displayed severe nephrotoxicity.

In 2021, Harris et al. synthesized a series of PMB analogues with different lipid components and scaffold sizes and also acquired data about their toxicity and potency. After such discovery, it was later understood that AMR not only originates from the envelope but also the ability of the bacteria to form biofilms using the cell surface component. Therefore, based on these potency and toxicity profiles on hand, analogues 9k and 9g were picked and re-synthesized for biofilm assay. The synthesis method was also developed as inspired from the synthesis of battacin analogues by Yim et al. (2020), which the peptide scaffold will be one-off generated from the Solid Phase Peptide Synthesis (SPPS) and modified with distinct lipid tail via a patented CLipPA chemistry of Brimble Laboratory to efficiently yield these two analogues. The synthesis was monitored accordingly to confirm the identity and purity of the product. Both 9k and 9g PMB analogues were successfully prepared with high purity (at least 96%) yet a relatively low yield (~17%). These products were sent to Dr. Richard Douglas (Faculty of Medical and Health Science, University of Auckland) to support the biofilm assay as part of the collaboration.

ROBERT MULLIN 
University of Auckland

Whakarāpopoto Rangahau I Summary of Research

Antimicrobial resistance (AMR) is defined as the ability of pathogenic organisms to survive the action of antibiotics. In OECD countries, up to 17% of all bacterial infections involve AMR, with a predicted 2.4 million to die from AMR infections globally by 2050. Due to systemic inequalities in Aotearoa New Zealand, Māori face higher rates of hospitalisation and therefore the threat of AMR impacts Māori disproportionately. The Polymyxin class of antibiotics destroy pathogenic bacteria by attacking their cell wall, a mechanism for which resistance is slow to develop. However, due to their well established kidney toxicity, they are unsuitable for widespread use. By modifying Polymyxin B, this project aims to produce new analogues which are less toxic to kidney organoids.

Research findings 

Antimicrobial resistance is an emerging, serious threat to global and NZ health. This means that current antimicrobial drugs will be less effective at fighting infections. This studentship focused on modifying a toxic antibiotic (Polymyxin B) that bacteria are less resistant to, to reduce its toxicity. Four versions of this antibiotic were made and are currently being tested for their ability to kill disease causing bacteria by researchers at the University of Otago. If the antibiotics are effective at killing bacteria, they will then undergo a series of tests to determine their toxicity. This could result in the development of a new antibiotic drug.

JACQUELINE ORMBSY
University of Canterbury 

Whakarāpopoto Rangahau I Summary of Research

The Rift Valley Fever virus is a disease endemic to Africa with high morbidity in young ruminants. The Rift Valley Fever virus is not present in Aotearoa New Zealand, although with a changing climate, this may change.

Recent research suggests that the protein RIOK3 is involved in mounting an anti-viral interferon response to the Rift Valley fever virus. When the virus attacks a cell, the RIOK3 protein is secreted, triggering antiviral gene transcription. RIOK3 is hypothesised to have a ubiquitin binding site that influences this behaviour. This project involves purification of RIOK3 and characterisation of the binding of RIOK3 to ubiquitin.

Research findings

Recent research has identified a protein known as RIOK3 that plays a key role in the human immune response to Rift Valley Fever Virus. This virus causes dangerous infections (almost 100% abortion rate and high mortality in livestock) and is listed by the World Health Organization as a virus that is likely to cause the next global pandemic. Understanding how RIOK3 operates could hold the key to developing effective treatments against this virus. However, there is still much that is not understood about how RIOK3 functions. One theory is that its activity is regulated through a process called ubiquitination. Interestingly, when the sequence of RIOK3 was first determined, significant differences from similar proteins in its family were identified, making its activity potentially more unique. In this study, the student and supporting research team attempted to produce RIOK3 in the lab for further investigation. While the full-length version of RIOK3 was successfully expressed using bacterial SHuffle E. coli cells, attempts to produce a truncated version were unsuccessful. Additionally, efforts to purify the full-length RIOK3 protein using specialized techniques yielded impure samples, hindering the team’s ability to conduct further experiments. Research efforts are now focused on refining purification methods to obtain a cleaner sample, which will enable a deeper delve into understanding how RIOK3 functions in combating viral infections. This research is a crucial step towards developing targeted therapies to combat the Rift Valley Fever Virus and other related viral infections.

TANIRA KINGI
MRINZ 

Whakarāpopoto Rangahau I Summary of Research

Addressing the inequities associated with SARS-CoV-2 vaccination efficacy, this research project aims to uncover the effectiveness of SC vs IM needle-lengths on the immunogenicity and reactogenicity of the bi-valent COVID-19 booster. Having been designed to be delivered IM, our current vaccination strategy does not account for the high levels of obesity amongst our country, and the inability for the needle to reach its desired target of the deltoid muscle. With high proportions of obesity amongst Māori and Pasifika populations in Aotearoa, vaccine immunogenicity and reactogenicity will be compared for in participants who receive a COVID-19 booster with 12.7mm needle (SC) vs 38mm needle (IM). Participants with BMI over 30.2 (women) and 37.3 (men) will be enrolled.

Research Findings

Previous research has shown standard needles often don’t reach the muscle for people with a larger habitus, however it isn’t known if this has impact on how the vaccine works. The student was involved in the beginning of an ongoing randomised controlled trial investigating the immune response and side effects of the COVID-19 vaccine booster when delivered into the muscle or into the fat directly under the skin. In total 486 participants will be enrolled for this study from pharmacy vaccination sites across the motu. During the student’s time at the MRINZ she developed study materials and assisted the team with essential documents for ethics approval, which is now in place.

During COVID-19 vaccination programme Māori and Pasifika whānau were the hardest to get vaccinated, for multiple reasons. Māori and Pasifika have high rates of large body habitus, related to the social determinants of health that impede on their health such as housing, access to healthy food, financial instability, and barriers to accessing healthcare. Therefore, they are at higher risk for incorrect vaccine delivery with current vaccination guidelines. If this study identifies differences in immunogenicity or reactogenecity, this may result in important changes in vaccination guidelines to clarify when a longer needle should be selected. During the student’s time at the MRINZ she developed study materials and assisted the team with essential documents for ethics approval, which is now in place, so recruitment could begin.

SAMANTHA SAMANIEGO
University of Auckland

Whakarāpopoto Rangahau I Summary of Research

The post-COVID era is characterised by changes in the epidemiology and clinical presentations of respiratory infections. One example is the increase in numbers of children presenting with complex pneumonia. Reasons for this increase in complex pneumonia cases are unknown.

Project aims:

·      Conduct a systematic review of the epidemiology and clinical presentation of childhood pneumonia, focusing on differences now to what occurred in the pre-COVID era;

·      Audit children hospitalised with complex pneumonia at Starship Children’s Hospital during 2023. This audit will inform the development of a case record form for a case:control study of risk factors for complex pneumonia.

Research Findings 

In Aotearoa New Zealand, childhood pneumonia hospitalisation rates, particularly among Pacific and Māori ethnic groups, are notably high. Complex pneumonia, a particularly severe form of pneumonia, involves complications like pleural empyema or effusion, when fluid fills the pleural cavity covering the surface of the lung. These present significant challenges in management, and post-COVID, cases have surged possibly due to altered immunity and pathogen dynamics. This summer studentship summarised existing literature on the epidemiology, clinical presentation, and management of complex pneumonia in children, especially focusing on differences between the pre-COVID and current eras within New Zealand. Through a thorough search of the MEDLINE (Ovid) database, 69 articles were reviewed from several different countries worldwide. Key findings include: (1) Complex childhood pneumonia cases increased with the introduction of PCV13 vaccination in many countries, (2) Indigenous populations face higher risk of complex pneumonia, (3) Children receiving ibuprofen before hospital admission are at increased risk (4) Children with poor continuity of primary care are at increased risk of complex pneumonia.

There are several different approaches to managing complex paediatric pneumonia, with substantial variation regarding the most suitable treatment approach. There was also an evident lack of research referring to the COVID-19 pandemic and how this has shaped experiences and responses to complex childhood pneumonia. These findings underscore the need for New Zealand-based research into childhood complex pneumonia, especially to understand differences between the pre-COVID and current eras. Such insights are vital for optimising outcomes, particularly in unique populations like New Zealand, which face disproportionate disease burdens and impacts from COVID-related lockdowns.

OLIVIA SLOANE
University of Otago

Whakarāpopoto Rangahau I Summary of Research

Understanding what students consider when deciding and considering taking part in a vaccine trial is important to optimise engagement and recruitment. This is particularly important for this study which explores alternative means of administering vaccines (including needleless options) and examines the effectiveness of these vaccines so that our communities can be assured of their effectiveness in the future. Those who benefit the most from vaccines include indigenous communities and in Aotearoa whānau Māori. This study aims to use qualitative methodologies to explore what students consider when approached to participate in a vaccine study. A Māori summer student will use qualitative methods to interview Māori students who may or may not have agreed to participate in this vaccine study to explore using thematic analysis their experiences of the process. She will be based with other summer students at Kōhatu Centre for Hauora Māori and co-supervised by a Māori paediatrican Dr Liza Edmonds. Once completed her findings will provide valuable information for researchers in the area of vaccine infectious preventable diseases to optimise indigenous participation in rangahau such as this.

Research Findings 

Many countries have low rates of diseases such as measles including Aotearoa (New Zealand). However, waning immunity is a potential threat to maintaining this, with increasing cases of measles infection in young adults despite 2 doses of measles, mumps, and rubella (MMR) vaccine. Alternative ways of delivering vaccines (by aerosol with no needle) and intradermal (micro-needle) are currently being investigated in the MAXXED MMR clinical trial. Future findings from the trial may optimise vaccine participation especially among whānau Māori.

Questionnaires were designed and distributed to current study participants (92) and eligible non-participants (100). Responses were received from 26 study participants and 19 non-participants. Those identifying as Māori ethnicity and consenting to a follow-up interview (6 participants; 1 non-participant) were interviewed via zoom using the hui process to explore their experiences of being invited to participate in a vaccine alternative administration trial. Overall themes arising from the interview transcripts were derived using NVivo software. Key themes that emerged were 1) whakawhanaungatanga (reciprocal relationships), 2) kōkihi (interest in innovation), 3) mātua ā-wheako (lived experience) , 4) tiakitanga (trust) and 5) ka mua ka muri (preconceived beliefs).

The findings of this qualitative study will be used to enhance the ability of the rangahau to optimise communication with and participation of Māori students in the 2024 recruitment round. Insights gained provide the opportunity to optimise a pro-equity approach in vaccine trials for whānau Māori with potential long-term benefits for whānau in Aotearoa.

The student was part of the Health Research Council- funded study “Measuring and Boosting Waning Immunity to Measles”, led by Professor McIntyre.

LENA CASSIN
University of Otago

Whakarāpopoto Rangahau I Summary of Research

As the coronavirus pandemic has had such a high impact on people’s lives and the virus is still prominent in both human and animal population it is very important to track the possible jumps between species. The corona spike protein is a highly mutating part of the virus and has been shown in the literature to only requires a small mutation to be able to bound to human cells. This project aims to figure out if spikes from pet of highly frequented animals from Aotearoa, such as cats, dogs, deers or pekapeka, are likely to mutate and infect the humans close to them to prevent the country from another coronavirus outbreak.

Research Findings

This project aimed to express and purify Spike glycoproteins from animal Coronaviruses to track possible mutations that could jump from animal to humans. It has been known for some time now that Coronaviruses can jump from one species to another and that some part of the protein are highly mutative. During this project the student and wider research team managed to express and purify an endemic bat spike protein (pekapeka) which were prepared for negative stain and will be taken to Australia for Cryo-EM (cryo-electron microscopy) imaging. Efforts were made to express and purify two more spikes from turkeys and bovines, unfortunately the yield of expression wasn't high enough for further investigation. These three proteins were expressed in the EXPI-CHO cell system but none of the spikes express the same way. Turkey and Bovine require more troubleshooting to be able to prepare them for Cryo-EM. These findings are important to prepare for new outbreaks of Coronavirus that could be resistant to current vaccines.

FEYA DURKIN
Victoria University of Wellington 

Whakarāpopoto Rangahau I Summary of Research

Wastewater is a rich source of information about infectious diseases circulating in the community. During the COVID-19 pandemic, wastewater samples provided insights into how the pandemic was progressing, including the amount of virus in different communities and how variants change over time. Less attention has been placed on sampling at smaller scales such as buildings, where it is likely that collection frequency and/or methodology needs to change. This project will investigate use of various types of sampling equipment, deployed at various distances and sampling intensities, for the collection of wastewater from a single building.

Research Findings

The student investigated the efficacy and practicality of small-scale wastewater-based epidemiology (WBE). WBE is a technique used to identify pathogens present in wastewater and has previously been used for such purposes as monitoring levels of SARS-CoV-2 (the virus that causes COVID-19 disease) within the population. Sampling is typically done at wastewater treatment plants to provide data for communities, allowing for unbiased and broad-scale infectious disease surveillance. In this project the student investigated and refined techniques for WBE for local-scale sampling, for example at the level of a single building. Such sampling could be useful, for example, to pinpoint the source of an infectious disease outbreak or confirm no infected individuals are present in a specific location. To this end, the student amd her research support team flushed animal faeces (cow, sheep and bird) in a building and collected wastewater samples 1-km downstream. This was done to mimic pathogen deposition by infected individuals using the toilet. Because individuals tend to only use the toilet sporadically during the day, a pathogen signal may only appear intermittently in wastewater, especially when few individuals in the population are infected. Or it may be that the pathogen signal diffuses widely in the wastewater sample and is detectable for extended time-periods. The team used molecular methods to detect bacteria associated with the animal species whose faeces were flushed, along with human-associated bacteria and viruses. They found that sampling method and frequency had important effects on detection probability. For example, SARS-CoV-2 was detected in 100% of samples that were collected nearly continuously across a 15-minute window, but only 79% of the time if a single sample was collected within that timeframe, revealing that pathogen signals can be extremely transient in wastewater. The project will provide improvements in the way wastewater sampling is conducted at small spatial scales.

TO'OA TOFAMAMAO BROWN
University of Otago  

Whakarāpopoto Rangahau I Summary of Research

Mucosal-associated invariant T (MAIT) cells are a subset of T cells that have similar qualities to innate effector T cells. Activation of MAIT cells can occur through the binding of their T cell receptor (TCR) and an antigen presented by an MHC class-I related (MR1) molecule. Nod-like receptors (NLRs) are pattern recognition receptors that are found on APCs. The Ussher lab study how NLR agonists can stimulate TCR-mediated MAIT cell activation. This project will continue analyse this relationship, looking at the importance of NLR signalling and whether it contributes to direct or indirect stimulation of MAIT cell activation.

Research Findings

Mucosal associated invariant T (MAIT) cells are a unique subset of immune cells that play an important role in our body’s antibacterial response. MAIT cells are abundant in the human body making up approximately 2.6% of the total T cell population in peripheral blood and are commonly found in mucosal sites, the liver, and gut. Research has shown the potential use of MAIT cells in future treatments such as vaccines and cancer immunotherapies. Before these MAIT cells can be used in such treatments, it is important to learn more about them and the effect that different molecules and chemicals have on them. The student developed a model where MAIT cells can be expanded outside of the body, in vitro. The student will continue to improve the model in their 2024 Honours project. Once this model is satisfactory, cytokines and chemicals can be added to the MAIT cells to assess if they have any effect on MAIT cell expansion and function.

IMOGEN MCNEILL
University of Otago  

Whakarāpopoto Rangahau I Summary of Research

Dinogunellins are a class of four toxic phospholipids found in the roe of four fish with a unique and modular structure. To date, they have only been extracted rather than synthesised, resulting in small quantities of compound and limiting the ability to test their properties. This project aims to build on ongoing research in the Green group by utilising a click-chemistry approach to synthesise a library of dinogunellin analogues and subsequently test their biological activity. As numerous other toxic natural compounds have demonstrated biological activity and drug-like properties, dinogunellins and analogues are anticipated to behave similarly, and therefore show serious promise as a starting point for developing drugs to fight infectious diseases.

Research Findings

New Zealand will always have to face serious infectious disease threats and will therefore require a range of effective drugs for these situations. Dinogunellins have a unique structure, especially with regard to the phosphoramidate bond, that strongly suggests that analogues will be biologically active and possess drug-like properties. Synthesis of a variety of analogues with the aim of finding a drug lead is a critical step in developing our understanding of these compounds. Moreover, the widespread availability of the starting materials necessary means that synthesis of dinogunellin analogues will not be limited by rarity or expense of the required building blocks. Combined with the straightforward click chemistry approach, the synthesis of these potentially very useful compounds is uncomplicated, easily replicated, and therefore remarkably useful for New Zealand's ability to respond to infectious disease threats.

CLAUDIA PRIDDY
University of Auckland  

Whakarāpopoto Rangahau I Summary of Research

Acute respiratory infections are the most common reason preschool-aged children present to primary care and are the most frequent cause of hospital admission in this age group. Within New Zealand, acute respiratory infection hospital admission rates are higher for tamariki Māori and for Pacific children and children living in socioeconomically deprived households.

Many acute respiratory infection hospitalisations are preventable or avoidable by access to high quality preventive and primary care. Access to such care varies greatly between population groups in New Zealand. One group with notably poorer access are rural Māori.

The aims of this project are to:

1.     To engage with waahine Māori at one or more kōhanga reo in the Waikato region.

2.     To engage in kōrero with these wāhine to gain an understanding of their experiences with chest infections in their tamariki and of their healthcare access decision making and utilisation.

3.     To use this information to help inform the development of child health services in the Waikato region.

This project will be conducted within the ARROW study. It will utilise qualitative research methodologies.

Research Findings 

The ARROW study is a clinical trial of a novel intervention that aims to prevent recurrent hospital admissions for wheezy chest infections. Te Niwha are funding a community and primary care component of this project in the Waikato, Auckland and Bay of Plenty region.

Wheezy chest infections are a very frequent cause of visits to GP practices and to hospitals. For Māori children wheezy chest infections are a more frequent cause of hospital admission than non-Māori children. Is this because of barriers to them accessing primary care or due to the quality of the primary care they receive?

This project will help our understanding of how healthcare is accessed by wāhine Māori for their tamariki nohinohi. This will help inform the development of healthcare delivery in the north Waikato region. This region is acknowledged by the children’s health team at Waikato Hospital as being one where healthcare delivery needs to be improved.

We aim to submit a draft/summary of the project findings in June 2025. This date aligns with the milestones and deliverables of the parent project (ARROW).

MYLES LANDON
University of Canterbury  

Whakarāpopoto Rangahau I Summary of Research

Malonyl-CoA Decarboxylase (MCD) is a crucial enzyme in the fatty acid biochemical pathway. MCD is responsible for the breakdown of malonyl-CoA to acetyl-CoA, which can be synthesised into new fatty acids and ultimately energy production. The regulation of MCD is highly integral to one’s health in controlling the concentrations of malonyl-CoA present within a cell. A mutated or defunct MCD can lead to serious health problems as the synthesis and transport processes for fatty acids will be stopped, leading to a lack of energy production and a build-up of fats, toxins, and waste products that can severely impact the cardiovascular system.

Coacervates are membranelles organelles that localise enzymes and their substrates to increase their relative concentrations and thus improve catalytic activity. Incorporating MCD and malonyl-CoA inside a coacervate increases the reaction leading to an increase in the fatty-acid biochemical pathways.

This project will give great insights into how coacervates can alter catalytic reactivity to be used in further health research.

Research Findings

This project aligns with Te Niwha's mission to ensure that Aotearoa has world-class research facilities and the capability to respond to the sudden event of an infectious disease threat. It is important for us here in Aotearoa as a small relatively isolated country to stay connected to and at the forefront of global health research. Using coacervates in the medical sector is very new and largely unexplored. This project will aim to provide critical research information on how enzymes such as MCD can be integrated with coacervates to alter catalytic activity, with the potential of being used in a medical sense to aid in both protection and recovery from enzyme-targeting diseases. This project will aim to ensure that our response to an infectious disease is treated equally among ethnicities and will take the diversity of our country, and the different effects diseases can have on our community into account. The critical information gathered by this research will be shared with the scientific community, with a particular focus on the Maori community to ensure that the knowledge can be applied throughout all our communities.

ABIGAIL KALONTANO 
MRINZ

Whakarāpopoto Rangahau I Summary of Research

The Medical Research Institute of New Zealand (MRINZ) is currently conducting an observational feasibility study in Aotearoa. Community pharmacies are mirroring the ESR-led GP sentinel surveillance programme, where pharmacy patients with influenza-like illness are invited to have a nasopharyngeal swab for viral testing.

Activities include literature review, scoping existing pharmacy and research infrastructure, and building international research connections. This project will involve research into the regulatory and ethical research requirements to run observational clinical trials in Pacific Island countries, as well as identifying funding opportunities for a future clinical trial in Pacific Island countries.

Research Findings

s the potential to enhance clinical research and strengthen national public health responses in Aotearoa and the wider Pacific by:

·      Exploring the feasibility of extending the respiratory surveillance program into the Pacific islands, helping establish essential public health surveillance systems in regions with limited research infrastructure. This could contribute to early detection of respiratory threat, improving response time and overall health outcomes for the pacific regions.

·      Supporting the development of sustainable research capabilities through assessment of the pharmacy and research infrastructure in the Pacific Islands, promoting cross-border collaboration that will enhance both local and regional public health efforts.

·      By investigating the ethical and regulatory requirements for conducting clinical trials in the Pacific Islands, this project will contribute to the development of culturally appropriate and region-specific guidelines.

·      The identification of funding opportunities for expanding the surveillance study into the Pacific Islands will lay the foundation for sustainable, long-term research projects that address respiratory health issues in underserved regions. This could lead to continued collaboration and the development of additional studies, enhancing the global understanding of respiratory diseases.

PAEPA TOHAIA
University of Otago 

Whakarāpopoto Rangahau I Summary of Research

This summer studentship aims to improve maternal immunisation coverage among Māori and Pacific hapū māmā, addressing significant health inequities in Aotearoa. Grounded in a Kaupapa Māori methodology, the project uses data that was collected from communities in Porirua and Gisborne to understand their specific vaccination needs and challenges. The research involves analysing data that were collected though key stakeholder interviews with midwives, nurses, immunisation coordinators, policy analysts and focus group hui with hapū māmā, ensuring that Māori and Pacific voices are prioritized throughout. This summer studentship will use direct content analysis of interview data to determine if online maps, that show where hapū māmā can be vaccinated, can be improved. By working with communities, the project seeks to develop effective strategies to enhance vaccine uptake and ultimately improve health outcomes for mothers and their pēpi. Additionally, providing improvement recommendations required for online maps of maternal vaccination providers will help focus website improvements to facilitate access to immunisation services, helping to establish a more robust vaccination framework that can be adapted during public health crises.

Research Findings

The research aims to address the health inequities faced by Māori and Pacific hapū māmā with regard to maternal immunisation coverage. The online maps will empower hapū māmā to access immunisation services more easily, thereby improving health outcomes for mothers and their pēpi. This will lead to more equitable access to preventative health services and reduce the high risks associated with infectious diseases. The expected outcomes of the project include increased maternal immunisation rates among Māori and Pacific communities and the enhancement of a user-friendly online map that can be used to guide hapū māmā in accessing vaccination services. By establishing a reliable maternal immunisation framework this project supports Te Niwha’s mission of building a world-class response to infectious disease threats. This framework not only addresses maternal health during non-pandemic times but also provides a foundation for rapid response during health crises, such as pandemics.

SUMANTA SAHA
University of Otago

Whakarāpopoto Rangahau I Summary of Research

Measles immunity is waning and the virus is re-emerging in previously measles-eliminated settings such as Aotearoa New Zealand. This project will inform policy and practice in New Zealand by generating knowledge about the waning of measles immunity, the effectiveness of alternative MMR-delivery methods in boosting measles immunity in young seronegative adults previously vaccinated with 2-doses of MMR vaccine, and the antibody responses to aerosolized MMR vaccine (proxy to measles exposure) in seropositive young adults.

Specifically: 

·      Determining the prevalence and determinants of measles non-immunity in university students who have been screened for vaccine-preventable diseases, including measles.

·      Examining the diagnostic accuracy of a locally available test used for screening measles immunity by comparing it with a gold-standard test used internationally.

·      Comparing antibody responses to alternate vaccination (aerosol and intradermal) delivery methods with traditional (intramuscular) administration in a randomized-controlled trial.

·      Identifying antibody-based correlates of protection against measles using a challenge approach whereby aerosolized measles-containing vaccine (MMR) is used as a proxy for wild measles virus exposure.

Final Research Summary 

JACK BLACKWOOD
University of Auckland 

Whakarāpopoto Rangahau I Summary of Research

As demonstrated by the COVID-19 pandemic, viruses pose a significant and persistent global health risk. There are currently no approved antivirals for the vast majority of viral infections and in most cases health professionals can only offer supportive care. For viral infections with clinically approved antivirals available, many are at risk of antiviral resistance. Traditional Pacific medicines and rongoā Māori have been used for many centuries and are centred around a more holistic model of healthcare, illustrated by Te Whare Tapa Wha (Durie, 1998) and the Fonofale models (Pulotu-Endemann & Tu'itahi, 2009) which are echoed throughout Pacific cultures. Despite widespread use of traditional Pacific medicines and rongoā Māori, very few studies have examined their antiviral activities.

With consultation and collaboration with our Māori and Samoan partners, this research will investigate rongoā Māori and traditional Samoan medicinal extracts to determine potential antiviral activities against harmful human viruses including influenza virus (flu), and herpes simplex virus (causes cold sores and infection-related blindness). The findings of this study will be shared with traditional medicine practitioners to help guide specific treatments for viral infections to tailor the care they provide.

Final Research Summary

MELEMAFI PORTER
Victoria University of Wellington 

Whakarāpopoto Rangahau I Summary of Research

Vaccination against SARS-CoV-2 is effective at reducing mortality and morbidity of COVID-19. Obesity can decrease the probability of intramuscular vaccine delivery due to increased thickness of the subcutaneous tissue at the deltoid vaccination site. New Zealand vaccination guidelines provide non-specific advice for needle length selection, stating that a 38mm should be selected for a “very large or obese person”. As clinical judgement must be used for these instructions, interpretation likely varies between vaccinators. It is currently unknown whether intramuscular delivery of COVID-19 vaccines is essential to achieve full therapeutic efficacy. Furthermore, reactogenicity is significantly lower for IM vaccination compared with SC delivery for almost all IM vaccines. Concern regarding adverse events following immunisations results in vaccine hesitancy and refusal, therefore inadvertent SC delivery may lead to vaccine avoidant behaviour. This proposed study will compare immunogenicity and reactogenicity of IM and SC COVID-19 vaccination.

Final Research Summary 

KATHARINA WOLF
University of Otago 

Whakarāpopoto Rangahau I Summary of Research

Acute osteoarticular infections (OAI) pose a significant threat to Australasian children with reported infections rates higher than in other OECD countries. Improved culture techniques and sensitive nucleic acid amplification assays have resulted in recognizing Kingella kingae as the leading cause in young children. Early identification of the disease-causing pathogen improves patient prognosis and reduces treatment duration and the possibility of long term sequalae. About 1/3 of cases have no microbiological diagnosis with current gold standard polymerase chain reaction (PCR) and culture. Blood cultures are routinely performed but less sensitive compared to culture from joint aspirates, however these are not routinely carried out due to their invasiveness. 

Our group are developing a liquid biopsy assay to detect K. kingae cell-free DNA (cfDNA) in a patient’s blood and urine. Pathogenic cfDNA can be concentrated from urine using K. kingae specific probes coupled to magnetic beads. The captured cfDNA can then be amplified and quantified with real-time PCR. This novel diagnostic assay can be routinely implemented leading to more targeted antibiotic treatment for OAI patients. It also has the potential to be a foundation for the detection of other infectious diseases, following development of specific primers and probes for different pathogenic microorganisms.

Final Research Summary

The overall impact of this project will be to improve the diagnosis of currently hard-to-diagnose infections. Both platforms can be used within a laboratory setting without disrupting current workflows. The platforms will allow for faster diagnosis which will improve antimicrobial stewardship as doctors may not need to start empirical treatment. The ability for these two platforms to be utilised in remote areas either within Aotearoa or in the Pacific is promising. A non-invasive diagnostic platform will be a significant advance, especially in diagnosing disease in tamariki where obtaining invasive samples can be very difficult.

BRITTANY MEAFOU
University of Canterbury

Whakarāpopoto Rangahau I Summary of Research

Systemic failures in drinking water systems can result in significant health risks. Aotearoa faces a major drinking water infrastructure deficit of ~$120-185bn by 2050. The quality of the drinking water network in Aotearoa is sub-optimal and presents a public health risk. This project will examine the association between unplanned drinking water network outages and enteric disease notifications using a case-crossover study design.

The exposure assessment will leverage three large drinking water datasets which have been collated, standardised and published over the last four years by the supervision team as part of multiple projects (including a Te Niwha project). These include data on the quality and material of each drinking water pipe in Aotearoa, the spatial extent of publicly-owned water networks and the collation of the only national longitudinal dataset of drinking water quality. Enteric disease data will be collected from national notification data which include campylobacteriosis, cryptosporidiosis, giardiasis, salmonellosis, and E. coli infections and associated socio-demographic information. Our study uses a case-crossover study design which compares exposure to unplanned water outages in “case” periods (a period likely associated with a disease notification) to “control” periods (a period not associated with a disease notification).

He Hiranga a Rangahau I Research Impact

Previous research funded by Te Niwha has shown that we may have underestimated the already substantial drinking water infrastructure deficit in Aotearoa. This current research is investigating the relationship between unplanned outages in the drinking water reticulation and enteric disease. If a significant relationship is detected between outages and either drinking water quality or enteric disease rates, the work could assist water suppliers with prioritising drinking water renewals. Additionally, the results could assist researchers and policy makers quantify the burden of disease associated with unplanned outages across Aotearoa – a significant step towards generating an updated burden of disease from drinking water estimate, in particular, the burden associated with the drinking water reticulation.

Final Research Summary 

JANAYA STEVENSON
University of Otago

Whakarāpopoto Rangahau I Summary of Research

Skin infections affect approximately one-third of the population, with New Zealand experiencing one of the highest infection rates among developed countries. Acinetobacter baumannii is an emerging pathogen that poses a significant threat in healthcare settings, particularly due to its role in skin and soft tissue infections. This bacterium is notorious for its ability to develop resistance to multiple antibiotics, making infections difficult to treat. A. baumannii skin infections are often associated with severe outcomes, especially in patients with compromised immune systems or chronic wounds.

The rising incidence of antibiotic-resistant strains exacerbates the challenge, leading to increased morbidity, prolonged hospital stays, and higher healthcare costs. Addressing this issue requires urgent research into novel therapeutic targets and effective treatment strategies. We aim to identify key regulatory genes and pathways in a highly virulent A. baumannii strain using state-of-the-art sequencing techniques. Transposon sequencing (Tn-seq), a method that uses transposon insertion mutants to determine the fitness of genes on a genome-wide scale, will be employed to identify essential genes using a saturated Tn-seq library pool from A. baumannii Ab5075 in an in vitro biofilm and in vivo skin abscess model. Our innovative approach to determining essential genes will determine possible drug targets for treating skin infections. This research will focus on three key objectives:

1.     identifying genes required for bacterial survival in biofilms

2.     determining genes required for bacterial survival in a skin abscess model, and

3.     validating these gene targets to identify therapeutic targets.

Te Hiranga a Rangahau I Research Impact

Antimicrobial resistance (AMR) is major global threat, contributes to an increased number of deaths and health expenditure in every country around the globe. AMR causes millions of deaths per year, irrespectively of socioeconomic status. Antibiotic consumption has been implicated as a key driver for AMR, with recent evidence showing that animal consumption and AMR in food-producing animals have significant associations between humans and animals in critical high priority pathogens identified by the World Health Organization (WHO). The 2022 Global Burden of Disease report identified that A. baumannii as one of the emerging pathogens causing the fifth highest death count in New Zealand (171 / 100,000 people) [20]. A. baumannii is increasingly found to be resistant to available antibiotics. We believe, if AMR is not recognized by our society as a major infectious disease threat, common infections and minor surgeries will become untreatable and impact our lives. This project will enhance the understanding of treating infectious diseases and provide an innovative methodology to identify new drug targets. The overarching goal of this research project is to find and expose new drug targets in an emerging skin pathogen and develop new methods and strategies to treat complex bacterial infections.

Final Research Summary

MATIJA-TAAITOA SUCICH
University of Auckland

Whakarāpopoto Rangahau I Summary of Research

This study aims to:

• Use co-designed methods and tikanga to collect and extract medicinal parts of tūpākihi, using mātauranga to guide us around the poisonous and medicinal properties of the plant;
• Examine tūpākihi extracts for antiviral activities (using viral plaque reduction assays) against herpes simplex virus type 1 (HSV-1), which causes cold sores;
• Examine tūpākihi extracts for anti-inflammatory activities in immune cell lines (i.e. using THP-1 derived macrophages and Jurkat T lymphocytes) and assess potential toxicity of tūpākihi extracts on these cells in vitro;
• Explore the potential mechanisms of action for any bioactivities identified above by examining the impacts of tūpākihi extracts on growth and inflammatory signalling pathways (using Western blots etc.);
• Share these results with our whānau, hapori and iwi through hui and wānanga.

Final Research Summary

Masters Scholarship 
JACKSON SMEED-TAUROA 

Whakarāpopoto Rangahau I Summary of Research

The first step to provide best practice recommendations for future pandemics, is to describe how current practices impact our whānau. Māori are a collectivist culture, and being present to care for their whānau is important for both the patient and their whānau. This study aims to understand how health professionals can ensure the well-being of whānau whose whānau member is being cared for in an ICU. 

Final Report Summary