James E. Ussher

James E. Ussher
University of Otago · Department of Microbiology and Immunology

MBChB, PhD, FRCPA

About

123
Publications
15,792
Reads
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3,846
Citations
Additional affiliations
February 2016 - May 2016
University of Otago
Position
  • Professor (Associate)
December 2013 - present
University of Otago
Position
  • Lecturer
November 2010 - November 2013
University of Oxford
Position
  • Oxford Nuffield Medical Fellow

Publications

Publications (123)
Article
Mucosal-associated invariant T (MAIT) cells are an abundant innate-like T lymphocyte population that are enriched in liver and mucosal tissues. They are restricted by MR1, which presents antigens derived from a metabolic precursor of riboflavin synthesis, a pathway present in many microbial species, including commensals. Therefore, MR1-mediated MAI...
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CD161(++) CD8(+) T cells represent a novel subset that is dominated in adult peripheral blood by mucosal-associated invariant T (MAIT) cells, as defined by the expression of a Vα7.2-Jα33 TCR, and IL-18Rα. Stimulation with IL-18+IL-12 is known to induce IFN-γ by both NK cells and, to a more limited extent, T cells. Here, we show the CD161(++) CD8(+)...
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Key Points The frequency of CD161++ MAIT cells is dramatically decreased in the blood of HIV-infected patients, and they are nonrecoverable with HAART. Gut sequestration and apoptosis in response to bacterial signals may, amongst others, be mechanisms that contribute to this.
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Mucosal-associated invariant T (MAIT) cells are an abundant antibacterial innate-like lymphocyte population. There are conflicting reports as to their fate in HIV infection. The objective of this study was to determine whether MAIT cells are truly depleted in HIV infection. In this case-control study of HIV-positive patients and healthy controls, q...
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Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell population involved in anti-bacterial immunity. In human beings, MAIT cells are abundant, comprising ~10% of the CD8⁺ T-cell compartment in blood. They are enriched at mucosal sites and are particularly prevalent within the liver. MAIT cells are defined by the expression of a sem...
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Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive i...
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Vaginitis presentations are common, but traditional diagnostic methods are imperfect. Molecular methods for bacterial vaginosis (BV) and vulvovaginal candidiasis (CV) are increasingly available but not commonly utilized in Aotearoa New Zealand. We evaluated the Hologic Aptima BV and CV/Trichomonas vaginalis (TV) assays against our current methods (...
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Introduction There are multiple ongoing outbreaks of carbapenem resistant Acinetobacter baumannii (CRAb) infection in Fiji’s hospitals. CRAb is able to colonize and persist on various hospital surfaces for extended periods. We conducted a study to understand the extent of hospital environmental contamination and phylogenetic links with clinical iso...
Preprint
Full-text available
Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive i...
Article
Case This article reports a case of a 72-year-old man with bilateral total hip joint replacements who suffered cuts to his hands while butchering a wild boar. He presented to the emergency department with fevers and unilateral hip pain. Erysipelothrix rhusiopathiae ( E . rhusiopathiae ) was isolated on hip aspirate and blood cultures. E . rhusiopat...
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The Two Weeks in the World research project has resulted in a dataset of 3087 clinically relevant bacterial genomes with pertaining metadata, collected from 59 diagnostic units in 35 countries around the world during 2020. A relational database is available with metadata and summary data from selected bioinformatic analysis, such as species predict...
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Background Carbapenem resistant Acinetobacter baumannii (CRAb) is categorised by the World Health Organization (WHO) as a pathogen of critical concern. However, little is known about CRAb transmission within the Oceania region. This study addresses this knowledge gap by using molecular epidemiology to characterise the phylogenetic relationships of...
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This study examined the correlation between intestinal protozoans and the bacterial microbiome in faecal samples collected from 463 patients in New Zealand who were diagnosed with gastroenteritis. In comparison to traditional microscopic diagnosis methods, Multiplexed-tandem PCR proved to be more effective in detecting intestinal parasites. Among t...
Article
The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naïve at the time they were boosted. This adult cohort of 298 participants...
Preprint
Full-text available
The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naive at the time they were boosted. This adult cohort of 298 participants...
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Emerging SARS-CoV-2 variants pose a threat to human health worldwide. SARS-CoV-2 receptor binding domain (RBD)-based vaccines are suitable candidates for booster vaccines, eliciting a focused antibody response enriched for virus neutralizing activity. Although RBD proteins are manufactured easily, and have excellent stability and safety properties,...
Article
Background: In 2019, Aotearoa New Zealand (NZ) experienced its worst measles outbreak since 1997. Due to declining childhood vaccination rates since the beginning of the SARS-CoV-2 pandemic, NZ is at serious risk of another major measles outbreak. Our laboratory provides diagnostic services to NZ's Southern region. In 2019 the Southern region expe...
Preprint
The antigen presenting molecule, MR1, presents microbial metabolites to MAIT cells, a population of innate-like, anti-microbial T cells. It also presents an unidentified ligand to MR-1 restricted T cells in the setting of cancer. The cellular co-factors that mediate MR1 antigen presentation have yet to be fully defined. We performed a mass spectrom...
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The following article, Harrison, S., Baker, M.G., Benschop, J. et al. One Health Outlook 2, 4 (2020), was published online by BMC on31 January 2020 at: https://doi.org/10.1186/s42522-020-0011-0. It is © The Author(s) 2020, but is Open Access and is distributedunder the terms of the Creative Commons Attribution 4.0 International License (http://crea...
Article
Aim: To compare detection of SARS-CoV-2 from paired nasopharyngeal swabs (NPS) and saliva using molecular methods in common use for testing swabs in New Zealand. Method: Samples from individuals testing positive for SARS-CoV-2 in Auckland, Wellington and Dunedin were tested at the local laboratories using methods previously established for these...
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Background There is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease. Methods This prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for Māori, Pacific peoples, older adult...
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Antimicrobial resistance (AMR) is an increasing global threat that affects human, animal and, often less acknowledged, environmental health. This complex issue requires a multisectoral One Health approach to address the interconnectedness of humans, animals and the natural environment. The prevalence of AMR in these reservoirs varies widely among c...
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Background There is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease. Methods This prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for Māori, Pacific peoples, older adult...
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SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has wreaked havoc across the globe for the last two years. More than 300 million cases and over 5 million deaths later, we continue battling the first real pandemic of the 21st century. SARS-CoV-2 spread quickly, reaching most countries within the first half of 2020, and New Zealand was n...
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The rapid global rise of COVID-19 from late 2019 caught major manufacturers of RT-qPCR reagents by surprise and threw into sharp focus the heavy reliance of molecular diagnostic providers on a handful of reagent suppliers. In addition, lockdown and transport bans, necessarily imposed to contain disease spread, put pressure on global supply lines wi...
Article
Aim: To assess the sensitivity and potential utility of five RATs and the IDNow, Liat and Oxsed nucleic acid amplification tests (NAATs) in our population. Method: 39 retrospective and contrived SARS-CoV-2 positive samples were tested in parallel by standard RT-PCR and RAT. A second group of 44 samples was tested by standard RT-PCR, rapid RT-PCR...
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It has been 20 months since we first heard of SARS-CoV-2, the novel coronavirus detected in the Hubei province, China, in December 2019, responsible for the ongoing COVID-19 pandemic. Since then, a myriad of studies aimed at understanding and controlling SARS-CoV-2 have been published at a pace that has outshined the original effort to combat HIV d...
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During the first wave of SARS-CoV-2 infection in New Zealand a cohort of 78 PCR-confirmed COVID-19 cases was recruited in the Southern District Health Board region. Here we report on this unique cohort nearly 1-year after infection. There was no known community transmission in the region over the study period due to New Zealand’s elimination status...
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Objectives The incidence of infections with ESBL-producing Escherichia coli (ESBL-Ec) in New Zealand is increasing. ESBL-Ec most commonly cause urinary tract infections and are seen in both community and hospitalized patients. The reason for the increasing incidence of ESBL-Ec infections is unknown. Methods In this study, 65 urinary ESBL-Ec isolat...
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At the end of 2019 a newly emerged betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of severe pneumonia, subsequently termed COVID-19, in a number of patients in Wuhan, China. Subsequently, SARS-CoV-2 rapidly spread globally, resulting in a pandemic that has to date infected o...
Article
During New Zealand’s first outbreak in early 2020 the Southern Region had the highest per capita SARS-CoV-2 infection rate. Polymerase chain reaction (PCR) testing was initially limited by a narrow Case definition and limited laboratory capacity, and cases may have been missed. Our objectives were to evaluate the Abbott SARS-CoV-2 IgG nucleocapsid...
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Objectives Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS‐CoV‐2 antibodies. This study explored antibody responses in recovered COVID‐19 patients in a setting where the probability of re‐exposure is effectively nil, owing to New Zealand's suc...
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New Zealand has avoided the major health impacts of the SARS-CoV-2 pandemic due to a strict country-wide lockdown, the end-goal of which was elimination rather than mitigation and suppression. The New Zealand government’s use of scientific expertise, spanning public health, infectious diseases, genomics, modeling and immunology, has been one of the...
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Bacteria harbour multiple innate defences and adaptive CRISPR–Cas systems that provide immunity against bacteriophages and mobile genetic elements. Although some bacteria modulate defences in response to population density, stress and metabolic state, a lack of high-throughput methods to systematically reveal regulators has hampered efforts to unde...
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Full-text available
Mucosal associated invariant T (MAIT) cells are anti‐microbial innate‐like T cells that are abundant in blood and liver. MAIT cells express a semi invariant T cell receptor (TCR) that recognises a pyrimidine ligand, derived from microbial riboflavin synthesis, bound to MR1. Both blood and liver derived (ld)‐MAIT cells can be robustly stimulated via...
Preprint
Full-text available
Objectives Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS-CoV-2 antibodies. This study explored antibody responses in recovered COVID-19 patients in a setting where the probability of re-exposure is effectively nil, owing to New Zealand’s suc...
Article
Mucosal associated invariant T (MAIT) cells have a recognised innate-like capacity for antibacterial host defence, consequent on the specificity of their T cell receptor (TCR) for small molecule metabolites produced by a range of prokaryotic and fungal species, their effector memory phenotype, and their expression of cytotoxic molecules. However, r...
Preprint
Full-text available
Background During New Zealand’s first outbreak in early 2020 the Southern Region had the highest per capita SARS-CoV-2 infection rate. PCR testing was initially limited by a narrow case definition and limited laboratory capacity, so cases may have been missed. Objectives To evaluate the Abbott ® SARS-CoV-2 IgG nucleocapsid assay, alongside spike-b...
Article
Aim: To assess whether trimethoprim remains an appropriate empiric treatment for uncomplicated cystitis in women 15-55 years old. Methods: General practitioners in Auckland, Nelson-Marlborough, Otago and Southland were invited to participate in this audit of current practice. Participating general practitioners were asked to submit urine to the...
Article
The multidrug-resistant Staphylococcus capitis NRCS-A clone is responsible for sepsis in preterm infants in neonatal intensive care units (NICUs) worldwide. Here, to retrace the spread of this clone and to identify drivers of its specific success, we investigated a representative collection of 250 S. capitis isolates from adults and newborns. Bayes...
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Data on causes of community-onset bloodstream infection in Myanmar are scarce. We aimed to identify etiological agents of bloodstream infections and patterns of antimicrobial resistance among febrile adolescents and adults attending Yangon General Hospital (YGH), Yangon, Myanmar. We recruited patients ≥12 years old with fever ≥38°C who attended YGH...
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COVID-19 will be with us through the remainder of 2020 and almost certainly beyond. New Zealand needs a viable strategy to protect its populace until a vaccine is developed and in wide use. Until that time, it makes sense to protect the population by putting in place treatments that will be safe and effective, such as the use of convalescent sera a...
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Background A S. capitis strain called NRCS-A (S. capitis NRCS-A) has emerged as a cause of bloodstream infections and sepsis in neonatal intensive care units (NICUs) worldwide. Aim To identify risk factors for S. capitis NRCS-A colonisation among neonates, Dunedin Hospital NICU, Dunedin, New Zealand, from September 2013 through March 2015. Method...
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Background: A proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed "early clearance." Methods: Indonesian household contacts of TB cases were teste...
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Full-text available
Mucosal‐associated invariant T (MAIT) cells are innate‐like T lymphocytes that are abundant in mucosal tissues and the liver where they can respond rapidly to a broad range of riboflavin producing bacterial and fungal pathogens. Neutrophils, which are recruited early to sites of infection, play a non‐redundant role in pathogen clearance and are cru...
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Full-text available
There is increased recognition that complex health challenges at the human-animal-environmental interface require a transdisciplinary, “whole-of-society” approach. This philosophy is particularly pertinent in Aotearoa-New Zealand because of the country’s relatively isolated island ecosystem, economic reliance on agriculture and its intensification,...
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Full-text available
Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells which can be stimulated either via their T cell receptor (TCR) or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also c...
Article
Mucosal‐associated invariant T (MAIT) cells and Vδ2+ γδ T cells are anti‐bacterial innate‐like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control of infection. However, the role of ILLs in community‐acquired pneumonia (CAP) is unknown. Using sputum samples from a well‐characterised CAP cohort, MAIT cell a...
Article
Full-text available
Mucosal-associated invariant T (MAIT) cells can be activated via either their T cell receptor (TCR), which recognizes MR1-bound pyrimidines derived from microbial riboflavin biosynthesis, or via cytokines. These two modes of activation may act in concert or independently, depending upon the stimulus. It is unknown, however, how MAIT cell responses...
Article
Full-text available
MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel...
Preprint
Full-text available
Mucosal associated invariant T (MAIT) cells are innate like T lymphocytes that are abundant in mucosal tissues and the liver where they can respond rapidly to a broad range of riboflavin producing bacterial and fungal pathogens. Neutrophils, which are recruited early to sites of infection, play a non redundant role in pathogen clearance and are cru...
Article
Background: Early clearance of Mycobacterium tuberculosis is the eradication of infection before an adaptive immune response develops. We aimed to identify host factors associated with early clearance. Methods: Indonesian household contacts patients with smear-positive tuberculosis (TB) had an interferon-γ release assay (IGRA) at baseline and 14...
Preprint
Full-text available
Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells which can be stimulated either via their T cell receptor (TCR) or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also c...
Article
Background: Legionnaires' disease is under-diagnosed because of inconsistent use of diagnostic tests and uncertainty about whom to test. We assessed the increase in case detection following large-scale introduction of routine PCR testing of respiratory specimens in New Zealand. Methods: LegiNZ was a national surveillance study done over 1-year i...
Article
Background: Enteric fever is common in southeast Asia. However, there is little information on the circulating Salmonella enterica strains causing enteric fever in Myanmar. Methods: We performed antimicrobial susceptibility testing and whole genome sequencing on S. enterica bloodstream isolates from febrile patients aged ≥12 y attending two hosp...
Preprint
Full-text available
MAIT cells are an abundant innate-like T cell population which can be activated via either their T cell receptor (TCR), which recognizes MR1-bound pyrimidine antigens derived from microbial riboflavin biosynthesis, or via cytokines, such as IL-12 and IL-18. In vivo, these two modes of activation may act in concert or independently depending upon th...
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Full-text available
Background: Accurate estimates of typhoid disease burden are needed to guide policy decisions, including on vaccine use. Data on the incidence of enteric fever in Myanmar are scarce. We estimated typhoid and paratyphoid fever incidence among adolescents and adults in Yangon, Myanmar, by combining sentinel hospital surveillance with a healthcare ut...
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Full-text available
Immunopathology contributes to high mortality in tuberculous meningitis (TBM) but little is known about the blood and cerebrospinal fluid (CSF) immune response. We prospectively characterised the immune response of 160 TBM suspects in an Indonesian cohort, including 67 HIV-negative probable or definite TBM cases. TBM patients presented with severe...
Preprint
Full-text available
Background Mucosal-associated invariant T (MAIT) cells and Vδ2 ⁺ γδ T cells are anti-bacterial innate-like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control of bacterial infection. However, the role of ILLs in community-acquired pneumonia (CAP) is unknown. Methods Using sputum samples from a well-charac...