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Melbourne, Australia

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.

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. Source

Levy A.,PathWest Laboratory Medicine WA | Levy A.,University of Western Australia | Roberts J.,Doherty Institute | Roberts J.,RMIT University | And 11 more authors.
Journal of Clinical Virology

Background: Enterovirus D68 (EV-D68) has received considerable recent attention as a cause of widespread respiratory illness. Neurological syndromes such as acute flaccid paralysis following EV-D68 infection have also been reported in a small number of cases. Objectives: To summarize the clinical and epidemiological characteristics of laboratory confirmed EV-D68 cases in Australia. Study design: We combined EV-D68 data acquired through laboratory surveillance in Western Australia with cases from national enterovirus surveillance and regional acute flaccid paralysis (AFP) surveillance. Clinical data was obtained for EV-D68 cases and capsid protein sequences were used for phylogenetic analysis. Results: Sporadic cases of EV-D68 were recorded in Australia since 2008, with peaks in activity during 2011 and 2013. EV-D68 was primarily associated with respiratory disease, but was also detected in cerebrospinal fluid of one patient and faeces of two patients presenting with AFP. Conclusions: EV-D68 has been circulating in Western Australia and is likely to have also been present in the wider region for a number of years, causing primarily respiratory disease. Detection of EV-D68 in cerebrospinal fluid of one patient and in faeces of two AFP cases reinforces the association between EV-D68 and neurological disease. © 2015 Elsevier B.V. Source

Holmes J.A.,University of Melbourne | Congiu M.,University of Melbourne | Bonanzinga S.,Doherty Institute | Sandhu M.K.,University of Melbourne | And 11 more authors.
Alimentary Pharmacology and Therapeutics

Background The biological mechanism underlying the association between IFNL4/IFNL3 polymorphism and peginterferon/ribavirin (PR) response in HCV-1 is thought to involve differential intrahepatic interferon-stimulated gene expression. HCV-3 is more sensitive to PR, but there are no studies of the association between IFNL4 polymorphism, PR treatment response and liver interferon-stimulated gene expression in HCV-3. Aim We evaluated the association between IFNL4/IFNL3 genotypes, PR treatment outcomes and intrahepatic interferon-stimulated gene expression, according to HCV genotype. Methods HCV-1 and HCV-3 patients who received PR therapy were identified. IFNL3 (rs12979860) and IFNL4 genotype (rs368234815) were determined. A second cohort with stored liver specimens was identified. Expression of ISGs was measured by rt-PCR. Results Two hundred and fifty-nine patients were identified: 55% HCV-1, 45% HCV-3. IFNL4 genotype frequency was TT/TT 44%, TT/ΔG 42% andΔG/ΔG 14%. Linkage disequilibrium with IFNL3 genotype was high (r2 = 0.98). The association between IFNL4 genotype and PR response was attenuated in HCV-3 vs. HCV-1 (HCV-3: SVR 89% vs. 76% vs. 72% for TT/TT vs. TT/ΔG vs. ΔG/ΔG, P = 0.09; HCV-1: SVR: 82% vs. 29% vs. 24%, P < 0.001). Intrahepatic ISG expression was evaluated in 92 patients; 61% HCV-1. The association between IFNL4 genotype and liver ISG expression was significantly different for HCV-3 vs. HCV-1 (P-value for interaction = 0.046), with levels of interferon-stimulated gene expression being highest in HCV-1 patients who carried a poor-response IFNL4 genotype. Conclusions The relationship between IFNL4 genotype and PR treatment response as well as intrahepatic interferon-stimulated gene expression differs between HCV-1 and HCV-3. These data suggest fundamental differences in host-virus interactions according to HCV genotype. © 2015 John Wiley & Sons Ltd. Source

Worth L.J.,Doherty Institute | Worth L.J.,University of Melbourne | Spelman T.,Doherty Institute | Bull A.L.,Doherty Institute | And 3 more authors.
American Journal of Infection Control

Background The epidemiology of central line-associated bloodstream infections (CLABSI) in Australian intensive care units (ICUs) has not previously been reported. We sought to describe time-trends in CLABSI rates, infections by ICU peer-groups, etiology, and antimicrobial susceptibility of pathogens in a large cohort of Australian ICUs for the period January 1, 2009-December 31, 2013. Methods Using National Healthcare Safety Network methods, CLABSI surveillance in adult patients was performed by hospitals participating in the Victorian Healthcare Associated Infection Surveillance System (n = 29). Hospitals were grouped by location, sector, and teaching status. Results Overall, 384 CLABSI events were reported over 303,968 central venous catheter (CVC)-days, corresponding to a rate of 1.26/1,000 CVC-days (95% confidence interval, 1.14-1.40). Every 1-year increase was associated with a 26% reduction in CLABSI risk (risk ratio, 0.74, 95% confidence interval, 0.69-0.80; P <.001). The most frequently identified pathogens were Enterococcus spp (26.3%), followed by Candida spp (15.4%) and Staphylococcus aureus (13.3%). CLABSI due to Enterococcus spp, S aureus, and coagulase-negative Staphylococcus spp displayed significant reductions over time. Conclusions Internationally accepted surveillance methods have been employed in Australia, demonstrating CLABSI rates comparable to medical/surgical ICUs in the United States and a reduction in pathogen-specific infections over a 5-year period. © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Source

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

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. Source

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