Publications by authors named "Hiu Tat Chan"

21 Publications

  • Page 1 of 1

Novel Drexlerviridae bacteriophage KMI8 with specific lytic activity against Klebsiella michiganensis and its biofilms.

PLoS One 2021 7;16(9):e0257102. Epub 2021 Sep 7.

Department of Pharmacy and Biomedical Science, La Trobe Institute for Molecular Science, La Trobe University, Victoria, Australia.

The bacterial genus Klebsiella includes the closely related species K. michiganensis, K. oxytoca and K. pneumoniae, which are capable of causing severe disease in humans. In this report we describe the isolation, genomic and functional characterisation of the lytic bacteriophage KMI8 specific for K. michiganensis. KMI8 belongs to the family Drexlerviridae, and has a novel genome which shares very little homology (71.89% identity over a query cover of only 8%) with that of its closest related bacteriophages (Klebsiella bacteriophage LF20 (MW417503.1); Klebsiella bacteriophage 066039 (MW042802.1). KMI8, which possess a putative endosialidase (depolymerase) enzyme, was shown to be capable of degrading mono-biofilms of a strain of K. michiganensis that carried the polysaccharide capsule KL70 locus. This is the first report of a lytic bacteriophage for K. michiganensis, which is capable of breaking down a biofilm of this species.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257102PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423285PMC
September 2021

Pilot study of a combined genomic and epidemiologic surveillance program for hospital-acquired multidrug-resistant pathogens across multiple hospital networks in Australia.

Infect Control Hosp Epidemiol 2021 05 26;42(5):573-581. Epub 2020 Nov 26.

Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.

Objectives: To conduct a pilot study implementing combined genomic and epidemiologic surveillance for hospital-acquired multidrug-resistant organisms (MDROs) to predict transmission between patients and to estimate the local burden of MDRO transmission.

Design: Pilot prospective multicenter surveillance study.

Setting: The study was conducted in 8 university hospitals (2,800 beds total) in Melbourne, Australia (population 4.8 million), including 4 acute-care, 1 specialist cancer care, and 3 subacute-care hospitals.

Methods: All clinical and screening isolates from hospital inpatients (April 24 to June 18, 2017) were collected for 6 MDROs: vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp), and carbapenem-resistant Pseudomonas aeruginosa (CRPa) and Acinetobacter baumannii (CRAb). Isolates were analyzed and reported as routine by hospital laboratories, underwent whole-genome sequencing at the central laboratory, and were analyzed using open-source bioinformatic tools. MDRO burden and transmission were assessed using combined genomic and epidemiologic data.

Results: In total, 408 isolates were collected from 358 patients; 47.5% were screening isolates. ESBL-Ec was most common (52.5%), then MRSA (21.6%), vanA VRE (15.7%), and ESBL-Kp (7.6%). Most MDROs (88.3%) were isolated from patients with recent healthcare exposure.Combining genomics and epidemiology identified that at least 27.1% of MDROs were likely acquired in a hospital; most of these transmission events would not have been detected without genomics. The highest proportion of transmission occurred with vanA VRE (88.4% of patients).

Conclusions: Genomic and epidemiologic data from multiple institutions can feasibly be combined prospectively, providing substantial insights into the burden and distribution of MDROs, including in-hospital transmission. This analysis enables infection control teams to target interventions more effectively.
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http://dx.doi.org/10.1017/ice.2020.1253DOI Listing
May 2021

Lytic Bacteriophage EFA1 Modulates HCT116 Colon Cancer Cell Growth and Upregulates ROS Production in an Co-culture System.

Front Microbiol 2021 31;12:650849. Epub 2021 Mar 31.

Department of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Bendigo, VIC, Australia.

is an opportunistic pathogen in the gut microbiota that's associated with a range of difficult to treat nosocomial infections. It is also known to be associated with some colorectal cancers. Its resistance to a range of antibiotics and capacity to form biofilms increase its virulence. Unlike antibiotics, bacteriophages are capable of disrupting biofilms which are key in the pathogenesis of diseases such as UTIs and some cancers. In this study, bacteriophage EFA1, lytic against , was isolated and its genome fully sequenced and analyzed . Electron microscopy images revealed EFA1 to be a . The bacteriophage was functionally assessed and shown to disrupt biofilms as well as modulate the growth stimulatory effects of in a HCT116 colon cancer cell co-culture system, possibly via the effects of ROS. The potential exists for further testing of bacteriophage EFA1 in these systems as well as models.
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http://dx.doi.org/10.3389/fmicb.2021.650849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044584PMC
March 2021

Understanding occult hepatitis C infection.

Transfusion 2020 09 15;60(9):2144-2152. Epub 2020 Aug 15.

Research and Development, Australia Red Cross Lifeblood, Kelvin Grove, Queensland, Australia.

Background: Occult hepatitis C infection (OCI) is a type of hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells (PBMCs) and the absence of HCV RNA in serum.

Study Design And Methods: A literature review was conducted to identify articles that characterized OCI as a disease, including its epidemiology, mode of transmission, pattern of infection, progression, and treatment.

Results: OCI patients experience a milder degree of inflammatory and cirrhotic changes than patients with chronic hepatitis C. OCI is transmissible parenterally both in vivo and in vitro, however the duration and outcome of OCI remains unclear. OCI is most consistently found in patients with previous hepatitis C disease and hemodialysis patients. Beyond the at-risk populations, OCI has also been demonstrated among healthy individuals and blood donors.

Conclusions: This review summarises our current understanding of OCI and suggests areas for further research to improve our understanding of this phenomenon, including a better understanding of its epidemiology and full clinical course. The current understanding of OCI and its clinical implications remain limited. Further standardized detection methods, ongoing surveillance, and investigation of its potential transmissions are required.
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http://dx.doi.org/10.1111/trf.16006DOI Listing
September 2020

Characterization of Novel Lytic Bacteriophages of Isolated from a Pneumonia Patient.

Viruses 2020 10 8;12(10). Epub 2020 Oct 8.

Department of Pharmacy and Biomedical Science, La Trobe Institute for Molecular Science, La Trobe University, Bendigo, Victoria 3552, Australia.

spp. are becoming increasingly associated with lung infections in patients suffering from cystic fibrosis (CF). , which is closely related to , has been isolated from the lungs of CF patients and other human infections. This article describes the isolation, morphology and characterization of two lytic bacteriophages specific for an strain isolated from a pneumonia patient. This host strain was the causal agent of hospital acquired pneumonia-the first clinical report of such an occurrence. Full genome sequencing revealed bacteriophage genomes ranging in size from 45901 to 46,328 bp. Transmission electron microscopy revealed that the two bacteriophages AMA1 and AMA2 belonged to the family. Host range analysis showed that their host range did not extend to . The possibility exists for future testing of such bacteriophages in the control of infections such as those seen in CF and other infections of the lungs. The incidence of antibiotic resistance in this genus highlights the importance of seeking adjuncts and alternatives in CF and other lung infections.
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http://dx.doi.org/10.3390/v12101138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600146PMC
October 2020

Intraoral human herpes viruses detectable by PCR in majority of patients.

Oral Dis 2021 Mar 27;27(2):378-387. Epub 2020 Jul 27.

Department of Dermatology, Royal Melbourne Hospital, Melbourne, Vic., Australia.

Objectives: To identify factors which influence the intraoral prevalence of human herpes viruses (HHVs) using mucosal swabs, saliva samples and qPCR analysis.

Methodology: In this cross-sectional observational study, matched saliva and oral swabs were collected from a total of 115 subjects: 70 immunocompetent subjects with no mucosal abnormalities, 22 with mucosal abnormalities and 23 therapeutically immunocompromised individuals. Extracted DNA was analysed by multiplex qPCR for detection and quantification of HHVs 1-6.

Results: At least one human herpes virus was detected in 77.1% of immunocompetent individuals with no mucosal abnormalities, with EBV the most commonly detected at 61.4%. HHV-6 was detected in 17.1%, HSV-1 in 4.3% and CMV in 1.1%. Detection was higher in saliva than in oral swabs. There was no detection of HSV-2 or VZV. Neither presence of oral mucosal abnormality nor therapeutic immunocompromise was related to increased detection of human herpes virus.

Conclusion: Commensal detection rates of EBV are high, and caution in clinical correlation of positive detection is warranted. Commensal CMV rates are low, and detection is likely to be clinically relevant. This study presents a comprehensive commensal detection rate of HHVs 1-6 by qPCR in saliva and swabs.
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http://dx.doi.org/10.1111/odi.13523DOI Listing
March 2021

Novel Bacteriophages Capable of Disrupting Biofilms From Clinical Strains of .

Front Microbiol 2020 14;11:194. Epub 2020 Feb 14.

Department of Pharmacy and Biomedical Science, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia.

The increase in global warming has favored growth of a range of opportunistic environmental bacteria and allowed some of these to become more pathogenic to humans. is one such organism. Surviving in moist conditions in temperate climates, these bacteria have been associated with a range of diseases in humans, and in systemic infections can cause mortality in up to 46% of cases. Their capacity to form biofilms, carry antibiotic resistance mechanisms, and survive disinfection, has meant that they are not easily treated with traditional methods. Bacteriophage offer a possible alternative approach for controlling their growth. This study is the first to report the isolation and characterization of bacteriophages lytic against clinical strains of which carry intrinsic antibiotic resistance genes. Functionally, these novel bacteriophages were shown to be capable of disrupting biofilms caused by clinical isolates of The potential exists for these to be tested in clinical and environmental settings.
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http://dx.doi.org/10.3389/fmicb.2020.00194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033617PMC
February 2020

Australian consensus statements for the regulation, production and use of faecal microbiota transplantation in clinical practice.

Gut 2020 05 11;69(5):801-810. Epub 2020 Feb 11.

The University of Sydney, Sydney, New South Wales, Australia

Objective: Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications.

Design: For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed: donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

Results: Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include: (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development.

Conclusions: These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers.
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http://dx.doi.org/10.1136/gutjnl-2019-320260DOI Listing
May 2020

Bacteriophages in Natural and Artificial Environments.

Pathogens 2019 Jul 12;8(3). Epub 2019 Jul 12.

Department of Physiology, Anatomy & Microbiology, La Trobe University, Bundoora, VIC 3086, Australia.

Bacteriophages (phages) are biological entities that have attracted a great deal of attention in recent years. They have been reported as the most abundant biological entities on the planet and their ability to impact the composition of bacterial communities is of great interest. In this review, we aim to explore where phages exist in natural and artificial environments and how they impact communities. The natural environment in this review will focus on the human body, soils, and the marine environment. In these naturally occurring environments there is an abundance of phages suggesting a role in the maintenance of bacterial community homeostasis. The artificial environment focuses on wastewater treatment plants, industrial processes, followed by pharmaceutical formulations. As in natural environments, the existence of bacteria in manmade wastewater treatment plants and industrial processes inevitably attracts phages. The presence of phages in these environments can inhibit the bacteria required for efficient water treatment or food production. Alternatively, they can have a positive impact by eliminating recalcitrant organisms. Finally, we conclude by describing how phages can be manipulated or formulated into pharmaceutical products in the laboratory for use in natural or artificial environments.
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http://dx.doi.org/10.3390/pathogens8030100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789717PMC
July 2019

Genomic, morphological and functional characterisation of novel bacteriophage FNU1 capable of disrupting Fusobacterium nucleatum biofilms.

Sci Rep 2019 06 24;9(1):9107. Epub 2019 Jun 24.

Department of Pharmacy and Biomedical Sciences, La Trobe Institute for Molecular Science, La Trobe University, Victoria, Australia.

Fusobacterium nucleatum is an important oral bacterium that has been linked to the development of chronic diseases such as periodontitis and colorectal cancer. In periodontal disease, F. nucleatum forms the backbone of the polymicrobial biofilm and in colorectal cancer is implicated in aetiology, metastasis and chemotherapy resistance. The control of this bacteria may be important in assisting treatment of these diseases. With increased rates of antibiotic resistance globally, there is need for development of alternatives such as bacteriophages, which may complement existing therapies. Here we describe the morphology, genomics and functional characteristics of FNU1, a novel bacteriophage lytic against F. nucleatum. Transmission electron microscopy revealed FNU1 to be a large Siphoviridae virus with capsid diameter of 88 nm and tail of approximately 310 nm in length. Its genome was 130914 bp, with six tRNAs, and 8% of its ORFs encoding putative defence genes. FNU1 was able to kill cells within and significantly reduce F. nucleatum biofilm mass. The identification and characterisation of this bacteriophage will enable new possibilities for the treatment and prevention of F. nucleatum associated diseases to be explored.
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http://dx.doi.org/10.1038/s41598-019-45549-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591296PMC
June 2019

No evidence for widespread Babesia microti transmission in Australia.

Transfusion 2019 07 9;59(7):2368-2374. Epub 2019 May 9.

Research and Development, Australian Red Cross Blood Service, Brisbane, Queensland, Australia.

Background: A fatal case of autochthonous Babesia microti infection was reported in Australia in 2012. This has implications for Australian public health and, given that babesiosis is transfusion transmissible, has possible implications for Australian blood transfusion recipients. We investigated the seroprevalence of antibodies to B. microti in Australian blood donors and in patients with clinically suspected babesiosis.

Study Design And Methods: Plasma samples (n = 7,000) from donors donating in at-risk areas and clinical specimens from patients with clinically suspected babesiosis (n = 29) were tested for B. microti IgG by immunofluorescence assay (IFA). IFA initially reactive samples were tested for B. microti IgG and IgM by immunoblot and B. microti DNA by polymerase chain reaction.

Results: Although five donors were initially reactive for B. microti IgG by IFA, none was confirmed for B. microti IgG (zero estimate; 95% confidence interval, 0%-0.05%) and all were negative for B. microti DNA. None of the patient samples had B. microti IgG, IgM, or DNA.

Conclusions: This study does not provide evidence for widespread exposure to B. microti in Australian blood donors at local theoretical risk, nor does it provide evidence of B. microti infection in Australian patients with clinically suspected babesiosis. Given that confirmed evidence of previous exposure to B. microti was not seen, these data suggest that transmission of this pathogen is currently uncommon in Australia and unlikely to pose a risk to transfusion safety at present.
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http://dx.doi.org/10.1111/trf.15336DOI Listing
July 2019

Utilizing genomic analyses to investigate the first outbreak of vanA vancomycin-resistant Enterococcus in Australia with emergence of daptomycin non-susceptibility.

J Med Microbiol 2019 Mar 21;68(3):303-308. Epub 2019 Jan 21.

1 Victorian Infectious Diseases Service, Royal Melbourne Hospital, Melbourne, Australia.

Introduction: The majority of vancomycin-resistant Enterococcus faecium (VREfm) in Australia is of the vanB genotype. An outbreak of vanA VREfm emerged in our haematology/oncology unit between November 2014 and May 2015. The first case of daptomycin non-susceptible E. faecium (DNSEfm) detected was a patient with vanA VREfm bacteraemia who showed clinical failure of daptomycin therapy, prompting microbiologic testing confirming daptomycin non-susceptibility.

Objectives: To describe the patient profiles, antibiotic susceptibility and genetic relatedness of vanA VREfm isolates in the outbreak.

Methods: Chart review of vanA VREfm colonized and infected patients was undertaken to describe the demographics, clinical features and outcomes of therapy. Whole genome sequencing of vanA VREfm isolates involved in the outbreak was conducted to assess clonality.

Results: In total, 29 samples from 24 patients tested positive for vanA VREfm (21 screening swabs and 8 clinical isolates). Five isolates were DNSEfm (four patients colonized, one patient with bacteraemia), with only one patient exposed to daptomycin previously. In silico multi-locus sequence typing of the isolates identified 25/26 as ST203, and 1/26 as ST796. Comparative genomic analysis revealed limited core genome diversity amongst the ST203 isolates, consistent with an outbreak of a single clone of vanA VREfm.

Conclusions: Here we describe an outbreak of vanA VREfm in a haematology/oncology unit. Genomic analysis supports transmission of an ST203 vanA VRE clone within this unit. Daptomycin non-susceptibility in 5/24 patients left linezolid as the only treatment option. Daptomycin susceptibility cannot be assumed in vanA VREfm isolates and confirmatory testing is recommended.
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http://dx.doi.org/10.1099/jmm.0.000916DOI Listing
March 2019

Health service impact of testing for respiratory pathogens using cartridge-based multiplex array versus molecular batch testing.

Pathology 2018 Dec 30;50(7):758-763. Epub 2018 Oct 30.

Microbiology Department, Royal Melbourne Hospital, Melbourne, Vic, Australia; The University of Melbourne, Melbourne, Vic, Australia; Murdoch Children's Research Institute, Parkville, Vic, Australia.

There is increasing demand for access to rapid microbiological testing, with a view to improving clinical outcomes. The possibility of rapid testing has been facilitated by development of cartridge-based random access molecular technologies that are now widely available. Whether the expense of cartridge-based assays is justified in terms of clinical or laboratory cost savings is controversial. This prospective study evaluated the impact of the Biofire FilmArray Respiratory Panel ('FilmArray'), a cartridge-based random access molecular test, compared with standard batched molecular testing using an 'in-house' respiratory polymerase chain reaction (PCR) on laboratory and health service outcomes for adult patients at a tertiary-level adult hospital in Melbourne, Australia. Laboratory result turnaround time was significantly reduced with the FilmArray (median 4.4 h) compared to a standard validated in-house respiratory PCR assay (median 21.6 h, p < 0.0001) and there was a significant increase in diagnostic yield with the Filmarray (71/124, 57.3%) compared to in-house PCR (79/200; 39.5%; p = 0.002). Despite improved result turnaround time and increased diagnostic yield from testing, there was no corresponding reduction in hospital length of stay or use of isolation beds. Although cartridge-based molecular testing reduced turnaround time to result for respiratory pathogen testing, it did not impact on health service outcomes such as hospital length of stay. Further work is warranted to determine whether cartridge-based tests at the point of care can improve clinical and health service impacts.
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http://dx.doi.org/10.1016/j.pathol.2018.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111697PMC
December 2018

Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia.

Pharmaceuticals (Basel) 2018 Feb 26;11(1). Epub 2018 Feb 26.

Department of Pharmacy and Applied Science, La Trobe Institute for Molecular Science, La Trobe University Bendigo Campus, PO Box 199, Bendigo 3550, Australia.

The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases.
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http://dx.doi.org/10.3390/ph11010026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874722PMC
February 2018

Ross River virus in Australian blood donors: possible implications for blood transfusion safety.

Transfusion 2018 02 19;58(2):485-492. Epub 2018 Jan 19.

QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Background: Emerging transfusion-transmissible pathogens, including arboviruses such as West Nile, Zika, dengue, and Ross River viruses, are potential threats to transfusion safety. The most prevalent arbovirus in humans in Australia is Ross River virus (RRV); however, prevalence varies substantially around the country. Modeling estimated a yearly risk of 8 to 11 potentially RRV-viremic fresh blood components nationwide. This study aimed to measure the occurrence of RRV viremia among donors who donated at Australian collection centers located in areas with significant RRV transmission during one peak season.

Study Design And Methods: Plasma samples were collected from donors (n = 7500) who donated at the selected collection centers during one peak season. Viral RNA was extracted from individual samples, and quantitative reverse transcription-polymerase chain reaction was performed.

Results: Regions with the highest rates of RRV transmission were not areas where donor centers were located. We did not detect RRV RNA among 7500 donations collected at the selected centers, resulting in a zero risk estimate with a one-sided 95% confidence interval of 0 to 1 in 2019 donations.

Conclusion: Our results suggest that the yearly risk of collecting a RRV-infected blood donation in Australia is low and is at the lower range of previous risk modeling. The majority of Australian donor centers were not in areas known to be at the highest risk for RRV transmission, which was not taken into account in previous models based on notification data. Therefore, we believe that the risk of RRV transfusion transmission in Australia is acceptably low and appropriately managed through existing risk management, including donation restrictions and recall policies.
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http://dx.doi.org/10.1111/trf.14472DOI Listing
February 2018

Characterization and formulation into solid dosage forms of a novel bacteriophage lytic against Klebsiella oxytoca.

PLoS One 2017 17;12(8):e0183510. Epub 2017 Aug 17.

La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.

Aim: To isolate and characterize bacteriophage lytic for the opportunistic pathogen Klebsiella oxytoca and their formulation into a range of solid dosage forms for in-vitro testing.

Methods And Results: We report the isolation, genomic and functional characterization of a novel bacteriophage lytic for Klebsiella oxytoca, which does not infect the closely related Klebsiella pneumoniae. This bacteriophage was formulated into suppositories and troches and shown to be released and lyse underlying Klebsiella oxytoca bacteria in an in-vitro model. These bacteriophage formulations were stable for at least 49 days at 4°C.

Conclusions: The successful in-vitro assay of these formulations here suggests that they could potentially be tested in-vivo to determine whether such a therapeutic approach could modulate the gut microbiome, and control Klebsiella oxytoca overgrowth, during antibiotic therapy regimes.

Significance And Impact Of The Study: This study reports a novel bacteriophage specific for Klebsiella oxytoca which can be formulated into solid dosage forms appropriate for potential delivery in testing as a therapy to modulate gut microbiome during antibiotic therapies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183510PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560551PMC
October 2017

Hepatitis E virus RNA in Australian blood donations.

Transfusion 2016 12 25;56(12):3086-3093. Epub 2016 Sep 25.

Research and Development, The University of Queenslan, Brisbane, Queensland, Australia.

Background: Hepatitis E virus (HEV) poses a risk to transfusion safety. In Australia, locally acquired HEV is rare and cases are mainly reported in travelers returning from countries endemic for HEV. The risk posed by HEV to transfusion safety in Australia is unknown; therefore, we aimed to measure the rate of current HEV infection in Australian blood donations.

Study Design And Methods: A total of 14,799 blood donations were tested for HEV RNA by transcription-mediated amplification, with confirmatory testing by reverse transcription-polymerase chain reaction. Viral load quantification and phylogenetic analysis was performed on HEV RNA-positive samples.

Results: One (0.0068%; 95% confidence interval [CI], 0.0002%-0.0376%) sample was confirmed positive for HEV RNA, resulting in a risk of collecting a HEV-viremic donation of 1 in 14,799 (95% CI, 1 in 584,530 to 1 in 2,657). The viral load in this sample was approximately 15,000 IU/mL, and it was determined to be Genotype 3.

Discussion: Our finding of 1 in 14,799 Australian donations positive for HEV RNA is lower than that from many other developed countries; this is consistent with the relatively low seroprevalence in Australia. As this HEV RNA-positive sample was Genotype 3, it seems likely that this infection was acquired through zoonotic transmission, either within Australia or overseas in a developed nation. HEV has the potential to pose a risk to transfusion safety in Australia; however, additional, larger studies are required to quantify the magnitude of this risk.
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http://dx.doi.org/10.1111/trf.13799DOI Listing
December 2016

The infectious disease blood safety risk of Australian hemochromatosis donations.

Transfusion 2016 12 23;56(12):2934-2940. Epub 2016 Sep 23.

Australian Red Cross Blood Service, Perth, Western Australia, Australia.

Background: It has been suggested that blood donors with hereditary hemochromatosis may pose an increased infectious disease risk and adversely affect recipient outcomes. This study compares the infectious disease risk of whole blood (WB) donors enrolled as therapeutic (T) donors to voluntary WB donors to evaluate the safety of blood products provided by the T donors.

Study Design And Methods: This was a retrospective cohort study of all WB donations at the Australian Red Cross Blood Service who donated between January 1, 2011, and December 31, 2013, comparing a yearly mean of 11,789 T donors with 107,773 total donations and a yearly mean of 468,889 voluntary WB donors with 2,584,705 total donations. We compared postdonation notification of infectious illnesses, bacterial contamination screening results, and positive tests for blood borne viruses in T and WB donors.

Results: Rates of transfusion-transmissible infections in donations destined for component manufacture were significantly lower in therapeutic donations compared to voluntary donations (8.4 vs. 21.6 per 100,000 donations). Bacterial contamination (43.0 vs. 45.9 per 100,000 donations) and postdonation illness reporting (136.2 vs. 110.8 per 100,000 donations) were similar in both cohorts.

Conclusions: The Australian therapeutic venisection program enables T donors to provide a safe and acceptable source of donated WB that has a low infectious disease risk profile.
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http://dx.doi.org/10.1111/trf.13802DOI Listing
December 2016

Phagocytic efficiency of monocytes and macrophages obtained from Sydney blood bank cohort members infected with an attenuated strain of HIV-1.

J Acquir Immune Defic Syndr 2003 Dec;34(5):445-53

AIDS Research Unit, Monash University, Victoria, Australia.

Defective function of monocyte-derived macrophages contributes to HIV-1 pathogenesis. We found that phagocytosis of the opportunistic pathogens Mycobacterium avium complex and Toxoplasma gondii was impaired in monocytes obtained from individuals infected with wild-type strains of HIV-1 but generally not in monocytes collected over a 6-year period from Sydney Blood Bank Cohort (SBBC) members infected with nef/long terminal repeats (LTR) region-defective strains of HIV-1. However, longitudinal analysis of phagocytosis in 1 SBBC member, C54, showed the development of defective engulfment of opportunistic pathogens at the most recent time points, coincident with the development of further molecular deletions in the nef/LTR region. Another SBBC member, C98, underwent bronchoscopy, which provided material to examine phagocytic signaling in alveolar macrophages. In contrast to normal phagocytic efficiency of C98's monocytes (over a 6-year period), defective signaling events during FcgammaR-mediated phagocytosis by C98's alveolar macrophages were observed. High basal phosphorylation within HIV-infected macrophages correlated with colocalization of tyrosine-phosphorylated proteins with HIV-1 p24 antigen rather than around the phagocytic targets as observed in uninfected cells. Thus, although phagocytic efficiency appears to be generally unimpaired in monocytes from SBBC members, evidence of impairment in recent samples from 1 SBBC member, coincident with further genetic changes within the virus, and abnormal phagocytic signaling in alveolar macrophages from another SBBC member may herald loss of attenuation of those strains.
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http://dx.doi.org/10.1097/00126334-200312150-00001DOI Listing
December 2003
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