Ava Elsmore
University of Otago
Project title: What are the clinical characteristics of laboratory-confirmed influenza in children <16 years of age presenting to Christchurch Hospital?
Research priority: Diagnostics
Status: COMPLETED
Influenza in children causes much higher rates of hospitalisations, mortality and a highly variable clinical presentation compared with adults. This research aimed to identify the common clinical characteristics of children presenting to hospital with influenza infection.
Distinguishing influenza from influenza-like illnesses presenting with similar characteristics is an important area to address following the COVID-19 pandemic. The study identified risk factors and demographics associated with influenza severity, to improve efficiency of influenza diagnosis, and resource management in hospital. Traditionally Māori have been disproportionately affected by influenza and the study looked at ways to mitigate poor outcomes in our tamariki.
RESEARCH PERSONNEL
- Tony Walls | Primary Supervisor
- Milly Bowen | Secondary Supervisor
| Research findings Influenza virus can present through several different symptoms in children, making it difficult to distinguish between other flu-like illnesses and some serious ones. The focus of this research was to create a resource that makes it easier to recognize influenza symptoms in children. The data in this research was collected from patient medical notes using an anonymous list of children with laboratory-confirmed influenza who presented to Christchurch Hospital in 2022. This was an ideal year to observe symptoms due to Covid-19 as all patients were tested on admission. The main information we were interested in collecting was age, sex, and presenting symptoms. Other data collected included, ethnicity, length of admission, co-morbidities, Tamiflu antiviral, and antibiotics use. One of the main observations of this research found some presenting symptoms to be more closely associated with certain age brackets over others. For instance, fever was one of the most prevalent presenting symptoms in children 0-12, and upper respiratory tract infections were classified by cough and runny nose in children aged 13-15. Another common symptom that presented in younger age brackets included lower respiratory tract infections, classified by increased work of breathing. Within the study database of 305 children, 22.95% were Māori, 8.71% Pacific, and 43.9% NZ European. From ages 0- 15, the age bracket found to have the most confirmed cases was 5-10 years, and 1-3 years was identified as second. It was also interesting to note that the influenza antiviral Tamiflu was not commonly administered but there were high levels of antibiotic prescribing. |
Branagh Overington
Te Puna Ora o Mataatua (TPOOM)
Project title: Kowheori 19 (COVID-19), Kaupapa Māori approach to COVID-19 vaccinations
Research priority: Prevention
Status: COMPLETED
While COVID-19 infections and hospitalisations were significantly higher in Māori populations, Māori have been reluctant to get vaccinated against COVID-19. This project examined a year of Te Puna Ora o Mataatua (TPOOM) Māori COVID-19 vaccine data to understand the efficacy of mobile vaccinations. We hypothesised that:
- rural-living Māori were more likely to get vaccinated at a mobile site;
- that going mobile increased Māori vaccination rates;
- older Māori were more likely to get vaccinated than younger Māori; and
- a significant number of Māori vaccinated by TPOOM at mobile sites were not enrolled at a PHO.
This project formed the quantitative part of a COVID-19 project measuring the efficacy of going mobile (the qualitative component was funded by Ministry of Health).
RESEARCH PERSONNEL
- Melanie Cheung | Primary Supervisor
- Katrina Poppe | Secondary Supervisor
| Research findings Māori populations in Aotearoa experienced significantly higher rates of COVID-19 infections and hospitalizations compared to Pākehā populations. Despite this, vaccine hesitancy has been observed among Māori, particularly in the Eastern Bay of Plenty (EBOP) region, where vaccination rates have been among the lowest in the country. This research project examined the impact of Te Puna Ora o Mataatua’s (TPOOM) mobile vaccination program on Māori communities in the EBOP. The student analyzed vaccination data for over 6,000 Māori individuals, categorizing the data by age and domicile, to investigate the impact of mobile vaccination on increasing vaccine uptake in Māori communities. Results showed the mobile vaccination program was successful in increasing vaccine uptake, with 61.3% of Māori vaccinations administered at mobile clinics. Kaumatua were more likely to get vaccinated and those living in more rural areas were more likely to be vaccinated at mobile clinics. Data showed a significant proportion (18%) of Māori vaccinated by TPOOM were not enrolled with a Primary Health Organisation (P.H.O) and of these, 82% were vaccinated at a mobile clinic, highlighting the importance of mobile vaccination programs. This research contributes to the ongoing effort to reduce health disparities and improve health outcomes for Māori in New Zealand. |
Jessica Leong
University of Otago
Project title: Host histone deacetylase 2 during the influenza A virus induced innate immune response
Research priority: Diagnostics
Status: COMPLETED
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 PERSONNEL
- Assoc Prof Matloob Husian | Primary Supervisor
| 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. |
Elizabeth Chernysheva
University of Otago
Project title: A CRISPR-based diagnostic assay for Legionella longbeachae in human blood
Research priority: Diagnostics
Status: COMPLETED
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 PERSONNEL
- Prof Martin Kennedy | Primary Supervisor
- Dr Amy Scott-Thomas | Secondary Supervisor
| 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. |
Douglass Yee
AUT
Project title: School-age vaccinations: Changes in uptake over time and by children’s characteristics
Research priority: Prevention
Status: COMPLETED
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 PERSONNEL
- Lisa Meehan | Primary Supervisor
- Thomas Schober | Secondary Supervisor
| 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
Project title: Nga Hua Akoranga: Māori Solution for global problems learning from MIHI Māori mobile vaccination programme to achieve equity
Research priority: Prevention
Status: COMPLETED
This research project evaluated Māori experiences of the COVID-19 Vaccination Immunisation Programme. The project drew on a diverse range of viewpoints, including Māori service providers, partners, organisations (including funders and consumer experiences) to identify the challenges associated with establishing and maintaining a kaupapa Māori mobile COVID-19 vaccination service to achieve health equity for Māori.
The purpose of this project was to utilise the MIHI Mobile Vaccine clinic as a case study and a backdrop to evaluate the impact of governmental decision making on the design, development and roll out of a kaupapa Māori vaccine clinic. By drawing on a mixed method approach the researcher explored:
- the acceptability of this evaluation project to Māori stakeholders;
- what did it take to set up a Māori-responsive vaccine clinic in response to the COVID-19 pandemic?
- what do we learn from whanau who attended the MIHI clinics, and was the service they received acceptable?
- what did the process involved in the design, development and implementation of the MIHI Mobile Vaccine Clinics teach us about Māori-responsive health services?
- what blueprint does it offer for future vaccine clinics in Aotearoa?
This was a multi-phased mixed methods research project, with the Summer Student involved in phase 2 of the research project.
Phase 2: What did it take to set up a Māori responsive vaccine clinic in response to the COVID-19 pandemic? Documentary Analysis was used to identify and examine key communications that record the interactions between MIHI and stakeholders (including funders).
This method was utilised to document the processes involved in establishing a Kaupapa
Māori vaccine clinic within current funding bodies and models that provide context of the health system.
Inductive thematic analysis and frequency reporting will identify and highlight the barriers and enablers to structurally setting up a Māori-responsive approach inclusive of Te Ao Māori principles. The findings from this study will inform phase 3.
RESEARCH PERSONNEL
- Dr Maria Patu | Primary Supervisor
- Mau Te Rangimarie Clark | Secondary Supervisor
| Research findings The project reported on stakeholder experiences and whānau experience at the MIHI vaccination clinic. Stakeholders were identified as host agencies, and partner agencies (St John, IMAC), while services users or consumers were identified as whānau. Key findings included:
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Larissa Renfrew
Hapai Te Hauora
Project title: Community respiratory virus surveillance in preschool children
Research priority: Surveillance
Status: COMPLETED
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 PERSONNEL
- Selah Hart (Hapai) | Primary Supervisor
- Cinnamon Lindsay (Hapai) | Secondary Supervisor
| 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:
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Jinwei Sun
University of Auckland
Project title: New Daptomycins to treat infectious disease
Research priority: Therapeutics
Status: COMPLETED
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 PERSONNEL
- Assoc Prof Paul Harris | Primary Supervisor
- Dr Aimee Horsfall | Secondary Supervisor
| 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
Project title: Staphylococcus aureus isolates from Osteomyelitis in children
Research priority: Diagnostics
Status: COMPLETED
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 PERSONNEL
- Dr Simon Swift | Primary Supervisor
- Dr Christina Straub | Secondary Supervisor
| 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. |
Jesse Wijaya
University of Auckland
Project title: Development of polymyxin analogues to tackle antimicrobial resistance
Research priority: Therapeutics
Status: COMPLETED
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 PERSONNEL
- Distinguished Prof Dame Margaret Brimble | Primary Supervisor
- Dr Alan Cameron | Secondary Supervisor
- Dr Richard Douglas | Secondary Supervisor
| 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. |
