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Barr I.G.,Doherty Institute | Vijaykrishna D.,Doherty Institute | Vijaykrishna D.,National University of Singapore | Sullivan S.G.,Doherty Institute
Eurosurveillance | Year: 2016

Influenza B viruses make up an important part of the burden from seasonal influenza globally. The 2015 sea-son in Australia saw an unusual predominance of influ-enza B with a distinctive switch during the season from B/Yamagata/16/88 lineage viruses to B/Victoria/2/87 lineage viruses. We also noted significant differences in the age groups infected by the different B lineages, with B/Victoria infecting a younger population than B/Yamagata, that could not be explained by potential prior exposure. © 2016, European Centre for Disease Prevention and Control (ECDC). All rights reserved.

PubMed | Doherty Institute, Royal Melbourne Hospital, University of Melbourne and Austin Health
Type: Journal Article | Journal: The Analyst | Year: 2016

The Gram-positive bacterium, Staphylococcus aureus (S. aureus), is a major pathogen responsible for a variety of infectious diseases ranging from cellulitis to more serious conditions such as septic arthritis and septicaemia. Timely treatment with appropriate antibiotic therapy is essential to ensure clinical defervescence and to prevent further complications such as infective endocarditis or organ impairment due to septic shock. To date, initial antibiotic choice is empirical, using a best guess of likely organism and sensitivity- an approach adopted due to the lack of rapid identification methods for bacteria. Current culture based methods take up to 5 days to identify the causative bacterial pathogen and its antibiotic sensitivity. This paper provides proof of concept for a biosensor, based on interdigitated electrodes, to detect the presence of S. aureus and ascertain its sensitivity to flucloxacillin rapidly (within 2 hours) in a cost effective manner. The proposed method is label-free and uses non-faradic measurements. This is the first study to successfully employ interdigitated electrodes for the rapid detection of antibiotic resistance. The method described has important potential outcomes of faster definitive antibiotic treatment and more rapid clinical response to treatment.

Liang T.J.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Block T.M.,Baruch S Blumberg Institute | McMahon B.J.,Centers for Disease Control and Prevention | Ghany M.G.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | And 6 more authors.
Hepatology | Year: 2015

Hepatitis B virus (HBV) is a significant global pathogen, infecting more than 240 million people worldwide. While treatment for HBV has improved, HBV patients often require lifelong therapies and cure is still a challenging goal. Recent advances in technologies and pharmaceutical sciences have heralded a new horizon of innovative therapeutic approaches that are bringing us closer to the possibility of a functional cure of chronic HBV infection. In this article, we review the current state of science in HBV therapy and highlight new and exciting therapeutic strategies spurred by recent scientific advances. Some of these therapies have already entered into clinical phase, and we will likely see more of them moving along the development pipeline. Conclusion: With growing interest in developing and efforts to develop more effective therapies for HBV, the challenging goal of a cure may be well within reach in the near future. © 2015 by the American Association for the Study of Liver Diseases.

PubMed | Australian National University, Doherty Institute, Mycobacterium Reference Laboratory and University of Melbourne
Type: Journal Article | Journal: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease | Year: 2016

Victoria, Australia.To measure the level of Mycobacterium tuberculosis transmission in Victoria.Retrospective analysis of mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) typing profiles from all first M. tuberculosis complex (MTC) isolates obtained from patients residing in Victoria from 2003 to 2010 was performed. State TB reference laboratory records were matched with Department of Health notification records to obtain further laboratory, demographic, contact investigation, clinical and treatment data. These data were used to assign patients to one of four categories: 1) no epidemiological link, 2) possible link, 3) likely transmission event and 4) laboratory contamination.A total of 2377 MTC isolates were genotyped using 15-locus MIRU-VNTR. Of the 2298 M. tuberculosis isolates, 1029 (44.8%) had unique genotypic profiles and were considered epidemiologically unrelated, while 1269 (55.2%) isolates shared a profile with one or more other strains, defined as a genotypic cluster. Systematic investigation of all 268 genotypic clusters, including 24-locus MIRU-VNTR on selected isolates, led to a further 862 patients being classified as unrelated, bringing the total number of patients with no epidemiological links to 1891 (82.3%). Of the remaining patients, 294 (12.8%) were classified as having possible epidemiological links, 96 (4.2%) were classified as having known epidemiological links representing likely transmission events and 17 (0.7%) as the result of laboratory cross-contamination.There is considerable genotypic diversity among Victorian MTC isolates, and the level of transmission is low.

Allard N.L.,Doherty Institute | Allard N.L.,University of Melbourne | MacLachlan J.H.,Doherty Institute | MacLachlan J.H.,University of Melbourne | And 2 more authors.
Australian and New Zealand Journal of Public Health | Year: 2015

Objective: To estimate the level of access to diagnosis, management and treatment for people living with chronic hepatitis B (CHB) in Australia, and to identify the gaps in clinical care for people living with CHB. Methods: Analysis of publicly available population level data including infectious disease notifications, Medicare and Pharmaceutical Benefits Scheme utilisation data, census-based estimates of CHB prevalence and burden, and mathematical modelling. Results: In 2012, of the estimated 218,567 Australians living with CHB, 57% had been diagnosed, 17,367 people (8%) received recommended HBV DNA viral load testing (without treatment) and 10,987 (5%) received antiviral therapy. Conclusions: This analysis reveals substantial gaps in the cascade of care for CHB in Australia, most notably in diagnosis (with 43% undiagnosed) and in recommended yearly monitoring (87% not in care). The number receiving therapy represents only one-third of those estimated to require treatment to prevent progressive liver disease and liver cancer. Implications: These findings demonstrate that the majority of those affected are not receiving guideline-based care; highlight the need for improvements in opportunistic screening, engagement in care, and access to therapy; and provide a method to assess the impact of public health and clinical interventions in response to CHB over time. © 2015 Public Health Association of Australia.

Littlejohn M.,Doherty Institute | Locarnini S.,Doherty Institute | Yuen L.,Doherty Institute
Cold Spring Harbor Perspectives in Medicine | Year: 2016

Members of the family Hepadnaviridae fall into two subgroups: mammalian and avian. The detection of endogenous avian hepadnavirus DNA integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. The nonprimate mammalian members of the Hepadnaviridae include the woodchuck hepatitis virus (WHV), the ground squirrel hepatitis virus, and arctic squirrel hepatitis virus, as well as a number of members of the recently described bat hepatitis virus. The identification of hepatitis B viruses (HBVs) in higher primates, such as chimpanzee, gorilla, orangutan, and gibbons that cluster with the human HBV, aswell as a number of recombinant forms between humans and primates, further implies a more complex origin of this virus. We discuss the current theories of the origin and evolution of HBVand propose a model that includes crossspecies transmissions and subsequent recombination events on a genetic backbone of genotype C HBV infection. The hepatitis delta virus (HDV) is a defective RNAvirus requiring the presence of the HBV for the completion of its life cycle. The origins of this virus remain unknown, although some recent studies have suggested an ancient African radiation. The age of the association between HDV and HBV is also unknown. © 2016 Cold Spring Harbor Laboratory Press.

Bruggink L.D.,Doherty Institute | Moselen J.M.,Doherty Institute | Marshall J.A.,Doherty Institute
Intervirology | Year: 2016

The comparative molecular epidemiology of the related GII.P7-GII.6 and GII.P7-GII.7 noroviruses has not been examined in detail. ORF 1, ORF 2 and ORF 1/ORF 2 RT-PCR as well as sequencing and phylogeny analysis were carried out on faecal specimens from 873 gastroenteritis outbreaks in Victoria, Australia (2012-2014). There were 575 (66%) detected as positive for norovirus by means of ORF 1 RT-PCR and/or ORF 2 RT-PCR. Of these, 24 (4.2%) were GII.6 (ORF 2) outbreaks, 7 (1.2%) were GII.7 (ORF 2) outbreaks, and 1 outbreak (0.2%) involved both GII.6 (ORF 2) and GII.7 (ORF 2) noroviruses. The median age of patients identified with GII.6 (ORF 2) (84 years) was significantly different from that of patients identified with GII.7 (ORF 2) (39 years). ORF 2 GII.6 and ORF 2 GII.7 sequences were always associated with a GII.P7 ORF 1 sequence, and GII.P7 sequences fell into two clusters, with one corresponding to the GII.6 ORF 2 genotype and the other to the GII.7 ORF 2 genotype, thereby indicating that the ORF 1 has been evolving separately for the two viruses. Thus, two closely related noroviruses can have a markedly different incidence and epidemiology. © 2016 S. Karger AG, Basel.

MacLachlan J.H.,Doherty Institute | MacLachlan J.H.,University of Melbourne | Cowie B.C.,Doherty Institute | Cowie B.C.,University of Melbourne | Cowie B.C.,Royal Melbourne Hospital
Cold Spring Harbor Perspectives in Medicine | Year: 2015

The epidemiology of hepatitis B virus (HBV) infection is geographically diverse, with population prevalence, age and mode of acquisition, and likelihood of progression to chronic infection mutually interdependent. The burden of chronic HBV infection is increasingly being recognized, with cirrhosis and liver cancer attributable to HBV continuing to increase. The outcomes of chronic HBV infection are affected by a range of factors, including viral genotype, the presence of coinfections with other blood-borne viruses, and the impact of other causes of liver disease. The increased recognition of HBV infection as a leading cause of death globally has resulted in the development of new structures and policies at the inter- national level; immediate attention to implementing these strategies is now required. © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Bruggink L.D.,Doherty Institute | Dunbar N.L.,Doherty Institute | Marshall J.A.,Doherty Institute
Epidemiology and Infection | Year: 2015

Noroviruses are a major cause of gastroenteritis. Vaccine strategies against norovirus are currently under consideration but depend on a detailed knowledge of the capsid genotypes. This study examined the incidence of norovirus outbreaks in residential aged-care facilities in Victoria, Australia over one year (2013) and documented the (capsid) norovirus genotypes associated with these outbreaks. It was found that 65.0% of 206 outbreaks tested were associated with norovirus infection, thereby showing norovirus to be the major cause of viral gastroenteritis in residential aged-care facilities. Fifteen capsid (open reading frame 2) genotypes were identified as follows: GI.2 (0.9%), GI.3 (1.8%), GI.4 (3.7%), GI.6 (0.9%), GI.7 (0.9%), GI.8 (0.9%), GII.1 (0.9%), GII.2 (0.9%), GII.3 (1.8%), GII.4 (2009-like) (0.9%), GII.4 (2012) (48.6%), GII.4 (2012-like) (16.5%), GII.4 (unknown) (9.2%), GII.5 (2.8%), GII.6 (0.9%), GII.7 (0.9%), GII.13 (6.4%) and an as yet unclassified GII genotype (0.9%). Although GII.4 was the most common norovirus capsid genotype detected, the great diversity of norovirus genotypes in the elderly indicates vaccination strategies for this demographic are not straightforward. Copyright © 2015 Cambridge University Press.

PubMed | Fudan University and Doherty Institute
Type: Journal Article | Journal: Journal of hepatology | Year: 2016

Chronic infection with hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). HBV isolates worldwide can be divided into ten genotypes. Moreover, the immune clearance phase selects for mutations in different parts of the viral genome. The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype and adaptive mutations, as well as environmental factors. Core promoter mutations and mutations abolishing hepatitis B e antigen (HBeAg) expression have been implicated in acute liver failure, while genotypes B, C, subgenotype A1, core promoter mutations, preS deletions, C-terminal truncation of envelope proteins, and spliced pregenomic RNA are associated with HCC development. Our efforts to treat and prevent HBV infection are hampered by the emergence of drug resistant mutants and vaccine escape mutants. This paper provides an overview of the HBV life cycle, followed by review of HBV genotypes and mutants in terms of their biological properties and clinical significance.

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