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McVernon J.,Murdoch Childrens Research Institute | Nolan T.,Murdoch Childrens Research Institute | Richmond P.,University of Western Australia | Reynolds G.,ANU Medical School | And 5 more authors.
Pediatric Infectious Disease Journal | Year: 2012

Background: Neisseria meningitidis is a leading cause of meningitis and septicemia globally. Recent shifts in serogroup dominance in some settings highlight the desirability of polysaccharide-conjugate vaccines with broader meningococcal coverage than serogroup C vaccines in widespread use. Methods: We assessed the safety and immunogenicity of a single dose of meningococcal quadrivalent (A, C, W-135, Y) tetanus conjugate vaccine (TetraMen-T), administered at 1 year of age. A total of 378 children were randomized to 1 of 6 groups-5 received alternative formulations of TetraMen-T, the sixth licensed adjuvanted serogroup C conjugate vaccine (Neisvac-C). Solicited adverse event reports were collected from day 0 to 7 after vaccination and unsolicited and serious adverse event reports throughout study participation. Immunogenicity was assessed by serum bactericidal assays containing either a human (hSBA) or baby rabbit (rSBA) complement source before and 1 month after immunization. Results: All vaccine formulations were safe and well tolerated. Using the various measures of immunogenicity, no consistent relationships were observed between the dose of either polysaccharide or carrier and serogroup-specific response for any one antigen. The highest-dose vaccine provided optimal coverage for all 4 serogroups, with the percentage of recipients achieving hSBA titers ≥8 against each as follows: A, 92%; C, 96%; W-135, 71%; Y, 82% (corresponding proportions with rSBAs titers >8 all exceeded 90%). The investigational vaccines were less immunogenic against the serogroup C capsular polysaccharide than the licensed comparator. Conclusions: Studies are ongoing that will help to identify optimal scheduling of quadrivalent meningococcal conjugate vaccines, to facilitate their inclusion into national immunization programs seeking extended serogroup coverage against meningococci. © 2012 Lippincott Williams & Wilkins.

Theodoratos A.,Australian National University | Blackburn A.C.,Australian National University | Coggan M.,Australian National University | Cappello J.,Australian National University | And 3 more authors.
International Journal of Obesity | Year: 2012

Glutathione transferase Kappa (GSTK1-1) also termed disulfide bond-forming oxidoreductase A-like protein (DsbA-L) has been implicated in the post-translational multimerization of adiponectin and has been negatively correlated with obesity in mice and humans. We investigated adiponectin in Gstk1 -/- mice and surprisingly found no difference in the levels of total serum adiponectin or the level of high molecular weight (HMW) multimers when compared with normal controls. Non-reducing SDS-polyacrylamide gel electrophoresis and western blotting also showed a similar distribution of low, middle and HMW multimers in normal and Gstk1 -/- mice. Variation in adiponectin has been correlated with glucose tolerance and with the levels of phosphorylated AMP-kinase but we found similar glucose tolerance and similar levels of phospho 5-AMP-activated protein kinase in normal and Gstk1 -/- mice. Consequently, our findings suggest that GSTK1-1 is not absolutely required for adiponectin multimerization in vivo and alternate pathways may be activated in GSTK1-1 deficiency.International Journal of Obesity advance online publication, 17 January 2012; doi:10.1038/ijo.2011.267.

Marshall H.S.,Vaccinology and Immunology Research Trials Unit | Marshall H.S.,University of Adelaide | Richmond P.,University of Western Australia | Richmond P.,Telethon Kids Institute | And 10 more authors.
Pediatric Infectious Disease Journal | Year: 2015

Background: Group A streptococci (GAS) and other β-hemolytic streptococci (BHS) cause pharyngitis, severe invasive disease and serious nonsuppurative sequelae including rheumatic heart disease and post streptococcal glomerulonephritis. The aim of this study was to assess carriage rates and anti-streptococcal C5a peptidase (anti-SCP) IgG levels and identify epidemiologic factors related to carriage or seropositivity in Australian children. Methods: A throat swab and blood sample were collected for microbiological and serological analysis (anti-SCP IgG) in 542 healthy children aged 0-10 years. Sequence analysis of the SCP gene was performed. Serological analysis used a competitive Luminex Immunoassay designed to preferentially detect functional antibody. Results: GAS-positive culture prevalence in throat swabs was 5.0% (range 0-10%), with the highest rate in 5 and 9 years old children. The rate of non-GAS BHS carriage was low (<1%). The scp gene was present in all 22 isolates evaluated. As age of child increased, the rate of carriage increased; odds ratio, 1.14 (1.00, 1.29); P = 0.50. Geometric mean anti-SCP titers increased with each age-band from 2 to 7 years, then plateaued. Age, geographic location and number of children within the household were significantly associated with the presence of anti-SCP antibodies. Conclusions: Children are exposed to GAS and other BHS at a young age, which is important for determining the target age for vaccination to protect before the period of risk. © 2015 Wolters Kluwer Health, Inc.

Farrell G.,ANU Medical School
Journal of Gastroenterology and Hepatology (Australia) | Year: 2010

Among approximately 650 000 people who die from hepatocellular carcinoma (HCC) each year, at least two-thirds live in Asia. Efforts to improve early diagnosis and treatment have not yet impacted mortality. An Asia-Pacific Working Party convened in Hong Kong in June 2008 to consider ways to prevent HCC in this region. Separate reviews have summarized epidemiology of HCC, preventive approaches related to hepatitis B virus (HBV), hepatitis C virus (HCV) and non-viral liver diseases, and the role of surveillance to detect HCC at a curative stage. We now present Consensus Statements from these deliberations and reviews. As chronic hepatitis B is the most common cause of HCC in Asia, effective hepatitis B vaccination programs are the most important strategy to reduce HCC incidence. Prevention of HCV by screening blood donors, universal precautions against blood contamination in health-care settings and reducing HCV transmission from injection drug use are also vital. There is strong evidence that effective antiviral therapy to control HBV infection or eradicate HCV substantially reduces (but does not abolish) HCC risk. With hemochromatosis, family screening, early diagnosis and correcting iron overload to prevent liver fibrosis prevents HCC. There is currently insufficient evidence to give firm recommendations on alcohol, obesity/metabolic risk factors and other liver diseases. HCC surveillance for high-risk groups is recommended in individual cases but cost-effectiveness is not as high as infant hepatitis B vaccination and screening blood for HCV. Widespread application of HCC surveillance in Asia-Pacific countries depends on economic factors and health-care priorities. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Blackburn A.C.,Australian National University | Coggan M.,Australian National University | Shield A.J.,Australian National University | Shield A.J.,University of Canberra | And 9 more authors.
Laboratory Investigation | Year: 2011

Glutathione transferase kappa (GSTK1-1) is a highly conserved, mitochondrial enzyme potentially involved in redox reactions. GSTK1-1-deficient mice were generated to further study the enzyme's biological role. Reduced and total glutathione levels in liver and kidney were unchanged by GSTK1-1 deficiency and NADPH quinone oxidoreductase 1 expression was not elevated indicating that there is no general underlying oxidative stress in Gstk1 / mice. Electron microscopy of liver and kidney showed no changes in mitochondrial morphology with GSTK1-1 deficiency. The death of a number of Gstk1 / males with urinary tract problems prompted close examination of the kidneys. Electron microscopy revealed glomerular basement membrane changes at 3 months, accompanied by detectable microalbuminuria in male mice (albumin:creatinine ratio of 2.660.83 vs 1.130.20 mg/mmol for Gstk1 / and wild-type (WT), respectively, P0.001). This was followed by significant foot process effacement (40-55% vs 10% for Gstk1 / and WT, respectively) at 6 months of age in all Gstk1 / mice examined. Kidney tubules were ultrastructurally normal. Compared with human disease, the Gstk1 / kidneys show changes seen in glomerulopathies causing nephrotic syndrome. Gstk1 / mice may offer insights into the early development of glomerular nephropathies. © 2007 USCAP, Inc All rights reserved.

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