Among 42 gram-negative bloodstream isolates from inpatients in 3 hospitals in Yangon, Myanmar, admitted during July-December 2014, 16 (38%) were extended-spectrum β-lactamase-producing ...Enterobacteriaceae and 6 (14%) produced carbapenemase. The high prevalence of multidrug-resistant gram-negative bacteria raises concerns about the empiric treatment of patients with sepsis in Yangon.
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 countries and thus often requires a country-specific approach. In New Zealand (NZ), AMR and antimicrobial usage in humans are relatively well-monitored and -understood, with high human use of antimicrobials and the frequency of resistant pathogens increasing in hospitals and the community. In contrast, on average, NZ is a low user of antimicrobials in animal husbandry systems with low rates of AMR in food-producing animals. AMR in New Zealand’s environment is little understood, and the role of the natural environment in AMR transmission is unclear. Here, we aimed to provide a summary of the current knowledge on AMR in NZ, addressing all three components of the One Health triad with a particular focus on environmental AMR. We aimed to identify knowledge gaps to help develop research strategies, especially towards mitigating AMR in the environment, the often-neglected part of the One Health triad.
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 not an exception. Here, we describe the first isolation and characterization of SARS-CoV-2 variants during the initial virus outbreak in New Zealand. Patient-derived nasopharyngeal samples were used to inoculate Vero cells and, three to four days later, a cytopathic effect was observed in seven viral cultures. Viral growth kinetics was characterized using Vero and VeroE6/TMPRSS2 cells. The identity of the viruses was verified by RT-qPCR, Western blot, indirect immunofluorescence assays, and electron microscopy. Whole-genome sequences were analyzed using two different yet complementary deep sequencing platforms (MiSeq/Illumina and Ion PGM™/Ion Torrent™), classifying the viruses as SARS-CoV-2 B.55, B.31, B.1, or B.1.369 based on the Pango Lineage nomenclature. All seven SARS-CoV-2 isolates were susceptible to remdesivir (EC
values from 0.83 to 2.42 µM) and β-D-N
-hydroxycytidine (molnupiravir, EC
values from 0.96 to 1.15 µM) but not to favipiravir (>10 µM). Interestingly, four SARS-CoV-2 isolates, carrying the D614G substitution originally associated with increased transmissibility, were more susceptible (2.4-fold) to a commercial monoclonal antibody targeting the spike glycoprotein than the wild-type viruses. Altogether, this seminal work allowed for early access to SARS-CoV-2 isolates in New Zealand, paving the way for numerous clinical and scientific research projects in the country, including the development and validation of diagnostic assays, antiviral strategies, and a national COVID-19 vaccine development program.
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 during the beginning of the AIDS epidemic. This massive response started by developing strategies to not only diagnose individual SARS-CoV-2 infections but to monitor the transmission, evolution, and global spread of this new virus. We currently have hundreds of commercial diagnostic tests; however, that was not the case in early 2020, when just a handful of protocols were available, and few whole-genome SARS-CoV-2 sequences had been described. It was mid-January 2020 when several District Health Boards across New Zealand started planning the implementation of diagnostic testing for this emerging virus. Here, we describe our experience implementing a molecular test to detect SARS-CoV-2 infection, adapting the RT-qPCR assay to be used in a random-access platform (Hologic Panther Fusion® System) in a clinical laboratory, and characterizing the first whole-genome SARS-CoV-2 sequences obtained in the South Island, right at the beginning of the SARS-CoV-2 outbreak in New Zealand. We expect that this work will help us and others prepare for the unequivocal risk of similar viral outbreaks in the future.
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 successful elimination strategy.
Methods
A triplex bead‐based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3 and IgG4) responses against Nucleocapsid (N) protein, the receptor binding domain (RBD) and Spike (S) protein of SARS‐CoV‐2 was developed. After establishing baseline levels with pre‐pandemic control sera (n = 113), samples from PCR‐confirmed COVID‐19 patients with mild–moderate disease (n = 189) collected up to 8 months post‐infection were examined. The relationship between antigen‐specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE‐2 interaction.
Results
While most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were relatively stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4–8 months post‐infection. Anti‐RBD antibodies were strongly correlated with NAbs at all time points (Pearson's r ≥ 0.87), and feasibility of using finger prick sampling to accurately measure anti‐RBD IgG was demonstrated.
Conclusion
Antibodies to SARS‐CoV‐2 persist for up to 8 months following mild‐to‐moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.
This study shows that antibodies to SARS‐CoV‐2 persist for up to 8 months following mild‐to‐moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in New Zealand. The figure was created with BioRender.com.
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 variable‐α chain 7.2 ...(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+ T‐cell population is the primary T‐cell population triggered by this mechanism. Both CD161++Vα7.2+ and CD161++Vα7.2− T‐cell subsets responded to IL‐12+IL‐18 stimulation, demonstrating this response was not restricted to the MAIT cells, but to the CD161++ phenotype. Bacteria and TLR agonists also indirectly triggered IFN‐γ expression via IL‐12 and IL‐18. These data show that CD161++ T cells are the predominant T‐cell population that responds directly to IL‐12+IL‐18 stimulation. Furthermore, our findings broaden the potential role of MAIT cells beyond bacterial responsiveness to potentially include viral infections and other inflammatory stimuli.
Summary
MHC class I‐related gene protein (MR1) is a non‐polymorphic MHC class IB antigen‐presenting molecule that is the restricting molecule for mucosal‐associated invariant T (MAIT) cells, a ...prominent population of innate‐like antibacterial T cells. The MAIT cell–MR1 axis represents a new paradigm in antigen presentation, with the MR1 ligand derived from vitamin B compounds or their metabolic precursors. Many bacteria and some fungi produce the activating ligand for MR1. In evolution, MR1 is highly conserved in most, but not all, mammals. In humans and rodents it is expressed in a broad range of cell types, both haematopoietic and non‐haematopoietic, although cell surface expression has been difficult to detect. Although MR1 trafficking shares features with both the MHC class I and MHC class II pathways, it is distinct. Several strands of evidence suggest that the intracellular location where MR1 is loaded differs for soluble ligand and for ligand derived from intact bacteria. The regulation of MR1 surface expression may also vary between different cell types. This paper will review what is currently known about the expression and trafficking of MR1 and propose a model for the loading and trafficking of MR1.
MHC‐related protein 1 (MR1) is an evolutionarily conserved, non‐polymorphic MHC class IB molecule that is the restricting molecule for mucosal‐associated invariant T cells. This paper will review our current understanding of the expression, loading with ligand and trafficking of MR1.
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