Virulence determinants of infectious bursal disease virus

The very virulent (vv) pathotype of infectious bursal disease virus (IBDV) has spread rapidly throughout Europe, Asia, and the Middle East. Although Australia is currently unaffected, there remains the potential for incursion of an exotic isolate. The aim of this study was to identify putative virulence determinants of IBDV to facilitate the development of improved diagnostic assays for detection and characterisation of vvIBDV isolates. Sequencing of Indonesian vvIBDV Tasik94 revealed a unique substitution [ A�¨S222] in the hypervariable region (HVR) of viral protein (VP) VP2, which did not appear to impinge on virulence or antigenicity. Phylogenetic analyses indicated that Tasik94 was closely related to Asian and European vvIBDV strains. Extensive alignment of deduced protein sequences across the HVR of VP2 identified residuesI242 I256 and I294 as putative markers of the vv phcnotype. Comparison of the pathology induced by mildly-virulent Australian IBDV 002/73 and Indonesian vvIBDV Tasik94, revealed that histological lesions in the spleen, thymus and bone marrow were restricted to Tasik94-infected birds, suggesting the enhanced pathogenicity of vvIBDV might be attributed to replication in non-bursal lymphoid organs. The biological significance of the VP2 HVR in virulence was assessed using recombinant viruses generated by reverse genetics. Both genomic segments of Australian IBDV 002/73, and recombinant segment A constructs in which the HVR of 002/73 was replaced with the corresponding region of either tissue culture-adapted virus or vvIBDV (Tasik94), were cloned behind T7 RNA polymerase promoter sequences. In vitro transcription/translation of each construct resulted in expression of viral proteins. Co-transfection of synthetic RNA transcripts initiated replication of both tissue culture-adapted parental and recombinant viruses, however attempts to rescue non-adapted viruses in specific-pathogen-free (SPF) chickens were unsuccessful. Nucleotide sequence variation in the HVR of VP2 was exploited for the development of a new diagnostic assay to rapidly detect exotic IBDV isolates, including vvIBDV, using reverse transcription polymerase chain reaction (RT-PCR) amplification and Bmrl restriction enzyme digestion. The assay was capable of differentiating between endemic and exotic IBDV in 96% of 105 isolates sequenced to date.

Clinical, ethical and legal considerations in the treatment of newborns with non-ketotic hyperglycinaemia

Non-ketotic hyperglycinaemia (NKH) is a devastating neurometabolic disorder leading, in its classical form, to early death or severe disability and poor quality of life in survivors. Affected neonates may need ventilatory support during a short period of respiratory depression. The transient dependence on ventilation dictates urgency in decision-making regarding withdrawal of therapy. The occurrence of patients with apparent transient forms of the disease, albeit rare, adds uncertainty to the prediction of clinical outcome and dictates that the current practice of withholding or withdrawing therapy in these neonates be reviewed. Both bioethics and law take the view that treatment decisions should be based on the best interests of the patient. The medical-ethics approach is based on the principles of non-maleficence, beneficence, autonomy and justice. The law relating to withholding or withdrawing life-sustaining treatment is complex and varies between jurisdictions. Physicians treating newborns with NKH need to provide families with accurate and complete information regarding the disease and the relative probability of possible outcomes of the neonatal presentation and to explore the extent to which family members are willing to take part in the decision making process. Cultural and religious attitudes, which may potentially clash with bioethical and juridical principles, need to be considered.

Pharmacist assessment of adherence, risk and treatment in cardiovascular disease (PAART CVD)

Cardiovascular disease (CVD) accounts for 18% of disease burden in Australia, and 35% of deaths. Evidence- based management of CVD risk requires systematic consideration of individual risk factors and overall CVD risk, and a balanced approach to lifestyle modification, the optimal use of medicines, and medicines adherence.

This project examines a pHot model for primary prevention of CVD in community pharmacy aimed at improving quality of care. Pharmacists from ten pharmacies received training in CVD risk factor management and facilitating patient lifestyle modification.

They recruited 70 participants aged 50-74 years, taking medicines for blood pressure (BP) or cholesterol, and without diabetes or CVD, At baseline, research assistants conducted a clinical assessment of anthropometric and biomedical risk factors, and conducted interviews to examine health behaviours, medicines use and related issues. Data was analysed by a consultant pharmacist and summary reports produced, with recommendations and targets for risk reduction. These were addressed by patients and their community pharmacists over five monthly sessions. At follow up, the relative risk reduction for CVD onset over the next five years was 24%, contributed to by reductions in mean systolic BP (-7mmHg), diastolic PP (-5 mmHg), total:HDL cholesterol ratio (—0.2), waist circumference (—2cm in males, —0.7cm in females) and other risk factors.

Several key health behaviours improved, including diet quality and physical activity levels. Prevalence of non-adherence to cardiovascular medicines dropped by 1 6% to 22%.

The potential health benefits from this intervention need to be confirmed via larger, controlled clinical trials. Overall, this appears to be a feasible and potentially effective public health measure.

Optimising care for people with chronic disease : foreword

Chronic disease self-management emerged as an organised, formal entity in Australia in the 1980s, when a specific group-based program was introduced from the United States. This program, the Stanford Arthritis Self-Management Course, was promulgated in Australia and other countries by its creator, Professor Kate Lorig of Stanford University. The program showed much early promise, particularly with its dissemination and uptake by an enthusiastic non-government sector. Over subsequent years it has matured, and many other programs endeavouring to support patients to engage in self-management have been developed. In some ways, chronic disease self-management has become mainstream.1-3

Can we reduce disease burden from osteoarthritis?

♦ The comparison of disparate interventions for the prevention and management of osteoarthritis (OA) is limited by the quality and quantity of published efficacy studies and the use of disparate measures for reporting clinical trial outcomes.

♦ The “transfer to utility” technique was used to translate published trial outcomes into a health-related quality-of-life (utility) scale, creating a common metric which supported comparisons between disparate interventions.

♦ Total hip replacement (THR) and total knee replacement (TKR) surgery were the most effective treatments and also highly cost-effective, at estimated cost per quality-adjusted life-year (QALY) of $7500 for THR and $10 000 for TKR (best estimate).

♦ Other apparently highly cost-effective interventions were exercise and strength training for knee OA (< $5000/QALY), knee bracing, and use of capsaicin or glucosamine sulfate (< $10 000/QALY).

♦ The cost per QALY estimates of non-specific and COX-2 inhibitor non-steroidal anti-inflammatory drugs were affected by treatment-related deaths and highly sensitive to the discounting of life-years lost.

♦ OA interventions that have been shown to be ineffective (eg, arthroscopy) are targets for redistribution of healthcare resources.

♦ OA interventions which lack efficacy studies (eg, prevention programs) require further research to assist priority setting.

♦ The application of the Health-sector Wide model to OA demonstrates its role as an evidence-based model that can be successfully applied to identify marginal interventions — those to be expanded and contracted to reduce the expected burden of disease, within current healthcare resources.

Prevention of a chronic progressive form of experimental autoimmune encephalomyelitis by an antibody against mucosal addressin cell adhesion molecule-1, given early in the course of disease progression.

A role for α4 and β7 integrins in mediating leucocyte entry into the central nervous system in the multiple sclerosis (MS)-like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated. However, the individual contributions of their respective ligands mucosal addressin cell adhesion molecule-1 (MAdCAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-cadherin expressed on the blood-brain barrier has not been determined. In the present paper, it is shown that an antibody directed against MAdCAM-1, the preferential ligand for α4β7, effectively prevented the development of a progressive, non-remitting, form of EAE, actively induced by injection of myelin oligodendrocyte glycoprotein peptide (MOG(_35-55)) autoantigen. Combinational treatment with both anti-MAdCAM-1, VCAM-1, and intercellular adhesion molecule-1 (ICAM-1) (ligand for integrin lymphocyte function-associated antigen (LFA)-1) mAbs led to more rapid remission than that obtained with anti-MAdCAM-1 antibody alone. However, neither MAdCAM-1 monotherapy, nor combinational antibody blockade was preventative when administered late in the course of disease progression. In conclusion, MAdCAM-1 plays a major contributory role in the progression of chronic EAE and is a potential therapeutic target for the treatment of MS. Critically, antivascular addressin therapy must be given eaA role for alpha4 and beta7 integrins in mediating leucocyte entry into the central nervous system in the multiple sclerosis (MS)-like disease experimental autoimmune encephalomyelitis (EAE) has been demonstrated. However, the individual contributions of their respective ligands mucosal addressin cell adhesion molecule-1 (MAdCAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-cadherin expressed on the blood-brain barrier has not been determined. In the present paper, it is shown that an antibody directed against MAdCAM-1, the preferential ligand for alpha4beta7, effectively prevented the development of a progressive, non-remitting, form of EAE, actively induced by injection of myelin oligodendrocyte glycoprotein peptide (MOG(35-55)) autoantigen. Combinational treatment with both anti-MAdCAM-1, VCAM-1, and intercellular adhesion molecule-1 (ICAM-1) (ligand for integrin lymphocyte function-associated antigen (LFA)-1) mAbs led to more rapid remission than that obtained with anti-MAdCAM-1 antibody alone. However, neither MAdCAM-1 monotherapy, nor combinational antibody blockade was preventative when administered late in the course of disease progression. In conclusion, MAdCAM-1 plays a major contributory role in the progression of chronic EAE and is a potential therapeutic target for the treatment of MS. Critically, antivascular addressin therapy must be given early in the course of disease prior to the establishment of irreversible damage if it is to be effective, as a single treatment modality.

Why is type 2 diabetes such a serious risk factor for coronary heart disease in women?

Women with type 2 diabetes were found to display an altered distribution of body fat, higher resistance to the action of insulin, highly increased levels of tryglycerides and significant elevations in the level of plasminogen activator inhibiter. Concludes that interventions which enhance the action of insulin, such as exercise or drug therapy, should lower the risk of coronary heart disease in these women.

Development and evaluation of an ELISA for the detection and 3D antibodies to foot and mouth disease virus

A group specific ELISA (enzyme-linked immunosorbent assay) was developed to detect virus infection associated antibodies in the serum of animals infected with any serotype of foot and mouth disease virus. The assay was developed from non-infectious sources, and is therefore suitable for use in countries where FMDV is exotic.

Level of urbanization and noncommunicable disease risk factors in Tamil Nadu, India

Objective To investigate the poorly understood relationship between the process of urbanization and noncommunicable diseases (NCDs) through the application of a quantitative measure of urbanicity.

Methods We constructed a measure of the urban environment for seven areas using a seven-item scale based on data from the Census of India 2001 to develop an “urbanicity” scale. The scale was used in conjunction with data collected from 3705 participants in the World Health Organization’s 2003 STEPwise risk factor surveillance survey in Tamil Nadu, India, to analyse the relationship between the urban environment and major NCD risk factors. Linear and logistic regression models were constructed examining the relationship between urbanicity and chronic disease risk.

Findings
Among men, urbanicity was positively associated with smoking (odds ratio, OR: 3.54; 95% confidence interval, CI: 2.4–5.1), body mass index (OR: 7.32; 95% CI: 4.0–13.6), blood pressure (OR: 1.92; 95% CI: 1.4–2.7) and low physical activity (OR: 3.26; 95% CI: 2.5–4.3). Among women, urbanicity was positively associated with low physical activity (OR: 4.13; 95% CI: 3.0–5.7) and high body mass index (OR: 6.48; 95% CI: 4.6–9.2). In both sexes urbanicity was positively associated with the mean number of servings of fruit and vegetables consumed per day (P < 0.05).

Conclusion
Urbanicity is associated with the prevalence of several NCD risk factors in Tamil Nadu, India.

Multi-envelope HIV-1 vaccine devoid of SIV components controls disease in macaques challenged with heterologous pathogenic SHIV

A central obstacle to the design of a global HIV-1 vaccine is virus diversity. Pathogen diversity is not unique to HIV-1, and has been successfully conquered in other fields by the creation of vaccine cocktails. Here we describe the testing of an HIV-1 envelope cocktail vaccine. Six macaques received the vaccine, delivered by successive immunizations with recombinant DNA, recombinant vaccinia virus and recombinant envelope proteins. Following vaccination, animals developed a diversity of anti-envelope antibody binding and neutralizing activities toward proteins and viruses that were not represented by sequence in the vaccine. T-cells were also elicited, as measured by gamma-interferon production assays with envelope-derived peptide pools. Vaccinated and control animals were then challenged with the heterologous pathogenic SHIV, 89.6P. Vaccinated monkeys experienced significantly lower virus titers and better maintenance of CD4+ T-cells than unvaccinated controls. The B- and T-cell immune responses were far superior post-challenge in the vaccinated group. Four of six vaccinated animals and only one of six control animals survived a 44-week observation period post-challenge. The present report is the first to describe pathogenic SHIV disease control mediated by a heterologous HIV-1 vaccine, devoid of 89.6 or SIV derivatives.

The relationship between depression and cardiovascular disease

Evidence from epidemiological studies has established that depression is a risk factor for the development of cardiovascular disease (CVD) and that the comorbidity of depression with pre-existing CVD worsens the prognosis for sufferers of CVD. Depression has also been associated with other behaviours that impact on CVD, such as medication non-compliance, and an unwillingness to adopt an exercise program, that reduce the likelihood of successful rehabilitation from CVD. Published literature on the current knowledge of the association between depression and CVD is reviewed in this paper.

Theobroma cacao (cocoa) supplementation in the treatment of Non-alcoholic Steatohepatitis

Non-alcoholic Steatohepatitis (NASH) is a chronic disease that results from accumulation of fat within the liver that subsequently stimulates free radicals to damage the cells of the liver. Cocoa is a rich source of antioxidants and it was found that its consumption could slow the development of NASH.

Modelling of potential food policy interventions in Fiji and Tonga and their impacts on noncommunicable disease mortality

Background: To compare the likely costs and benefits of a range of potential policy interventions in Fiji and Tonga targeted at diet-related noncommunicable diseases (NCDs), in order to support more evidence-based decision-making.

Method: A relatively simple and quick macro-simulation methodology was developed. Logic models were developed by local stakeholders and used to identify costs and dietary impacts of policy changes. Costs were confined to government costs, and excluded cost offsets. The best available evidence was combined with local data to model impacts on deaths from noncommunicable diseases over the lifetime of the target population. Given that the modelling necessarily entailed assumptions to compensate for gaps in data and evidence, use was made of probabilistic uncertainty analysis.

Results: Costs of implementing policy changes were generally low, with the exception of some requiring additional long-term staffing or construction activities. The most effective policy options in Fiji and Tonga targeted access to local produce and high-fat meats respectively, and were estimated to avert approximately 3% of diet-related NCD deaths in each population. Many policies had substantially lower benefits. Cost-effectiveness was higher for the low-cost policies. Similar policies produced markedly different results in the two countries.

Conclusion: Despite the crudeness of the method, the consistent modelling approach used across all the options, allowed reasonable comparisons to be made between the potential policy costs and impacts. This type of modelling can be used to support more evidence-based and informed decision-making about policy interventions and facilitate greater use of policy to achieve a reduction in NCDs.

What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels

Objective To estimate the impact of achieving alternative average population alcohol consumption levels on chronic disease mortality in England.

Design A macro-simulation model was built to simultaneously estimate the number of deaths from coronary heart disease, stroke, hypertensive disease, diabetes, liver cirrhosis, epilepsy and five cancers that would be averted or delayed annually as a result of changes in alcohol consumption among English adults. Counterfactual scenarios assessed the impact on alcohol-related mortalities of changing (1) the median alcohol consumption of drinkers and (2) the percentage of non-drinkers.

Data sources Risk relationships were drawn from published meta-analyses. Age- and sex-specific distributions of alcohol consumption (grams per day) for the English population in 2006 were drawn from the General Household Survey 2006, and age-, sex- and cause-specific mortality data for 2006 were provided by the Office for National Statistics.

Results The optimum median consumption level for drinkers in the model was 5 g/day (about half a unit), which would avert or delay 4579 (2544 to 6590) deaths per year. Approximately equal numbers of deaths from cancers and liver disease would be delayed or averted (∼2800 for each), while there was a small increase in cardiovascular mortality. The model showed no benefit in terms of reduced mortality when the proportion of non-drinkers in the population was increased.

Conclusions Current government recommendations for alcohol consumption are well above the level likely to minimise chronic disease. Public health targets should aim for a reduction in population alcohol consumption in order to reduce chronic disease mortality.

The burden of disease and injury in Australia

This report provides an overview of results from the Australian Burden of Disease and Injury Study undertaken by the AIHW during 1998 and 1999. The Study uses the methods developed for the Global Burden of Disease Study, adapted to the Australian context and drawing extensively on Australian sources of population health data. It provides a comprehensive assessment of the amount of ill health and disability, the ‘burden of disease’ in Australia in 1996.

Mortality, disability, impairment, illness and injury arising from 176 diseases, injuries and risk factors are measured using a common metric, the Disability-Adjusted Life Year or DALY. One DALY is a lost year of ‘healthy’ life and is calculated as a combination of years of life lost due to premature mortality (YLL) and equivalent ‘healthy’ years of life lost due to disability (YLD). This report provides estimates of the contribution of fatal and non-fatal health outcomes to the total burden of disease and injury measured in DALYs in Australia in 1996.