A Study To Investigate Alternative Regimens For Pneumococcal Vaccination Of Infants In A Developing Country
Funder
National Health and Medical Research Council
Funding Amount
$1,622,210.00
Summary
Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccine is very expensive (approximately USD $200-infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver thi ....Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccine is very expensive (approximately USD $200-infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver this vaccine, which are safe and effective. A recent WHO-GAVI meeting to address impediments to the introduction of these vaccines in developing countries recognized the need to evaluate other regimens of Pnc conjugate vaccine as an important research priority. This study has been deliberately formulated with that need in mind. The site for this research is Fiji. Although health services are good, Pnc disease, particularly pneumonia, remains the commonest cause of childhood morbidity and mortality. Fiji has good vaccine coverage and was the first Pacific country to introduce Hib vaccine. The arrival of the new, expensive Pnc conjugate vaccine presents a dilemma for Fiji and many similar countries. The expense of this vaccine would consume a large portion of the health budget. This study has two components: 1. A Phase 2 immunogenicity study (involving 750 infants) to evaluate regimens using reduced numbers of doses of Pnc conjugate vaccine, and using timing of dosing and combinations with the Pnc polysaccharide (PS) vaccine that may be more suited to the epidemiology of Pnc disease in developing countries. 2. An epidemiological study will measure the burden of invasive Pnc disease and pneumonia in Fiji. This will be part of a global effort to address these issues, and will be used to develop rapid assessment tools for these diseases in developing countries. We will seek cofounding for this component.Read moreRead less
A Case Control Study Of Hypertension In The Setting Of Poverty, Overcrowding And Infection.
Funder
National Health and Medical Research Council
Funding Amount
$603,331.00
Summary
It is unclear why chronic diseases are emerging in regions of significant disadvantage, i.e. where people are not overweight, are physically active and relatively young. We aim to identify factors responsible for the development of high blood pressure in a region where there is overcrowding, poverty, and infection. Low cost strategies to modify risk and educate the community can then be developed to prevent the emergence of these diseases.
Development Of Improved Vaccine Strategies For Measles Using Plant-derived Edible Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$331,980.00
Summary
Measles is a highly contagious viral disease that is contracted via the respiratory tract. Severe infection may lead to complications such as otitis media, pneumonia, encephalitis. Despite our current vaccination strategy outbreaks still occur in Australia and measles is a major problem in developing countries. In developing nations the case fatality rate of measles is several hundred times that of developed nations. Over 800,000 children still die each year due to measles. Problems with the cur ....Measles is a highly contagious viral disease that is contracted via the respiratory tract. Severe infection may lead to complications such as otitis media, pneumonia, encephalitis. Despite our current vaccination strategy outbreaks still occur in Australia and measles is a major problem in developing countries. In developing nations the case fatality rate of measles is several hundred times that of developed nations. Over 800,000 children still die each year due to measles. Problems with the current vaccination strategy are: a) doesn't work in children less than 1 year of age, b) must be kept cold c) must be given by injection. We believe that a plant derived edible vaccine for measles will address the limitations of currently available vaccine i.e. we can give it children under the age of 1 year, it can be eaten and doesn't have to be kept cold.Read moreRead less
The Role Of Renin-angiotensin And Growth Factors In Developmental And Pathological Neovascularization In The Retina
Funder
National Health and Medical Research Council
Funding Amount
$342,562.00
Summary
In the normal retina of newborn babies, the blood vessels in the inner layers are not fully formed. These vessels are probably stimulated to grow by a reduction in retinal oxygen, which initiates the production of growth agents in retinal cells. Once the new vessels are formed the oxygen level of the retina becomes normal, and both the growth agents and blood vessel growth are reduced. A prolonged reduction in oxygen levels in the retina can have serious consequences for vision. Indeed, in some ....In the normal retina of newborn babies, the blood vessels in the inner layers are not fully formed. These vessels are probably stimulated to grow by a reduction in retinal oxygen, which initiates the production of growth agents in retinal cells. Once the new vessels are formed the oxygen level of the retina becomes normal, and both the growth agents and blood vessel growth are reduced. A prolonged reduction in oxygen levels in the retina can have serious consequences for vision. Indeed, in some eye diseases new blood vessel growth is excessive and the vessels are not properly formed, which leads to hemorrhage and ultimately blindness. Such events occur when the oxygen environment of premature babies is reduced after placement in high oxygen incubators. Also, in long-term diabetes, the oxygen levels of the retina falls as the retinal vessels become damaged. To understand the events that cause new vessel growth in retinal development and disease requires identification of the growth agents and their location in the retina. Very recently it has been found that the growth agent renin-angiotensin is made in the retina, and that its blockade in diabetic patients slows the progression of new retinal vessel growth. Renin-angiotensin is likely to cause its growth effects by increasing the production of other retinal growth agents. This proposal will study the role of renin-angiotensin and other growth agents in the developing newborn rat retina and in eye diseases. This information may lead to a further understanding of how blood vessels form in the retinas of newborn babies, and the production of new treatments for eye diseases characterized by blood vessel growth in the retina.Read moreRead less
Novel Molecules Underlying The Development Of Corticopetal And Corticofugal Pathways
Funder
National Health and Medical Research Council
Funding Amount
$289,250.00
Summary
The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this ....The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this project is to understand how some of the connections between the cortex and other brain areas are formed during development. To do this the project will combine modern molecular techniques with neuroanatomy to identify molecules that are expressed by specific populations of neurons during critical developmental stages. These molecules will then be misexpressed in order to determine whether they are important for the development of appropriate connectivity in the brain. A knowledge of the molecules that regulate the development of neuronal pathways is critical to understanding brain development. In the long term, it will also lead to the development of therapies for cases when the brain is damaged or does not develop appropriately due to disease or injury.Read moreRead less
Extracellular Acidosis And PH-modulating Drugs As Novel Therapies For Neuroprotection In Hypoxia/ischemia In The Newborn
Funder
National Health and Medical Research Council
Funding Amount
$452,310.00
Summary
Approximately 4 out of every 1000 babies suffer severe perinatal asphyxia (a period of a shortage of oxygen) during the birth process which carries with it a high risk of brain damage or death. Those babies surviving with a severe disability cost Australia $500,000,000 per annum in lifelong costs. With currently available methods, the presence of asphyxia is difficult to detect and hence prevention is often not possible. At present, there are no effective medications to treat asphyxia-related br ....Approximately 4 out of every 1000 babies suffer severe perinatal asphyxia (a period of a shortage of oxygen) during the birth process which carries with it a high risk of brain damage or death. Those babies surviving with a severe disability cost Australia $500,000,000 per annum in lifelong costs. With currently available methods, the presence of asphyxia is difficult to detect and hence prevention is often not possible. At present, there are no effective medications to treat asphyxia-related brain damage in babies. This study brings together a multi-disciplinary team driven by the clinical need to develop suitable strategies for neuroprotection in the developing brain. We will investigate the neuroprotective properties of the clinically relevant factor of acidosis and determine how acidosis influences neuroprotectant drugs. In the future, it is envisaged that this study will lead to rationally-based clinical trials aimed at improving neurodevelopmental outcomes for babies who suffer asphyxia and for infants who are victims of near-drowning or head trauma.Read moreRead less
Effect Of Prostaglandin E2 On The Periodontium And Alveolar Bone Formation
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
Dental disease affecting the supporting structures of teeth (the periodontium), is prevalent in our society. Periodontal disease results in destruction of bone around teeth, loosening of teeth, compromised chewing function, and tooth loss. Over the last twenty years reports into the effects of prostaglandin E2 (PGE2) on the skeleton have been divided and controversial. While historically PGE2 has been reported to promote bone resorption, more recently it has been demonstrated that when PGE is pl ....Dental disease affecting the supporting structures of teeth (the periodontium), is prevalent in our society. Periodontal disease results in destruction of bone around teeth, loosening of teeth, compromised chewing function, and tooth loss. Over the last twenty years reports into the effects of prostaglandin E2 (PGE2) on the skeleton have been divided and controversial. While historically PGE2 has been reported to promote bone resorption, more recently it has been demonstrated that when PGE is placed in contact with mandibular bone, adjacent to erupted teeth, new bone and cementum formation occurs. The ability of PGE2 to induce new bone formation indicates a potential use for PGE2 in the management of bone loss associated with periodontal diseases, and the formation of new bone around dental implants, and around teeth following orthodontic movement. Growth factors are active in healing and have valuable applications in augmenting wound repair. Osseous and dental tissues are rich in growth factors, and these factors are involved with the regulation of bone metabolism as well as tissue repair, thus the action of PGE2 on the periodontium is most likely regulated via these factors. Since regeneration of the periodontium is a fundamental goal of dentistry, any treatment which leads to predictable formation of new connective tissues and their long term stability would be a major clinical advance.Read moreRead less
Psychosocial Predictors Of Developing Breast Cancer In Women From High Risk Breast Cancer Families
Funder
National Health and Medical Research Council
Funding Amount
$593,875.00
Summary
Over the past 20 years, studies have highlighted the possible roles of stressful life events and distress, possibly mediated by social support and personality, in causing or speeding up the development of breast cancer. This possibility is of strong concern to consumers. To date, there have been few well designed, prospective studies of this issue. Furthermore, no previous studies have specifically targeted women at increased risk because of their family history. Over the past 7 years, it has be ....Over the past 20 years, studies have highlighted the possible roles of stressful life events and distress, possibly mediated by social support and personality, in causing or speeding up the development of breast cancer. This possibility is of strong concern to consumers. To date, there have been few well designed, prospective studies of this issue. Furthermore, no previous studies have specifically targeted women at increased risk because of their family history. Over the past 7 years, it has become possible to identify 2 breast cancer genes (BRCA1 and BRCA2). Female carriers of mutations in these genes with a strong family history have an estimated lifetime risk of between 35% and 85%. The Kathleen Cuningham Consortium for Research into Familial Breast Cancer (KConFab) was established 7 years ago to coordinate the collection of genetic, epidemiological and clinical data in Australian families with a dominantly inherited predisposition to breast cancer. Due to the high rate of breast cancer diagnoses in this group, and the systematic recruitment of large numbers of high risk women by KConFab, there is a unique and temporary opportunity to conduct a rigorous study to resolve this question, with sufficient numbers involved. The study is a world first, and will provide the best data to date in this area. If the study demonstrates a relationship between psychosocial factors and the development of breast cancer in women from high risk breast cancer families, subsequent identification of vulnerable individuals and the implementation of appropriate interventions may have a real impact on reducing morbidity and mortality in this population. Furthermore, the results may have implications for all women in reducing breast cancer incidence.Read moreRead less
Psychosocial Predictors Of Developing Breast Cancer In Women From High Risk Breast Cancer Families
Funder
National Health and Medical Research Council
Funding Amount
$337,018.00
Summary
Systematic review of the literature on psychosocial predictors of developing breast cancer has highlighted the possible roles of life events and distress, possibly mediated by social support and personality. To date there has been little prospective assessment of psychosocial factors in the development of breast cancer. Furthermore, no research in this area has specifically targeted women at increased risk because of their family history, nor explored whether the impact of psychosocial factors s ....Systematic review of the literature on psychosocial predictors of developing breast cancer has highlighted the possible roles of life events and distress, possibly mediated by social support and personality. To date there has been little prospective assessment of psychosocial factors in the development of breast cancer. Furthermore, no research in this area has specifically targeted women at increased risk because of their family history, nor explored whether the impact of psychosocial factors systematically varies according to genetic mutation status. Over the past 5 years it has become possible to isolate two breast cancer genes (BRCA1 and BRCA2). Female carriers of mutations in these susceptibility genes have an estimated lifetime risk of breast cancer of between 37% and 85%. The Kathleen Cuningham Consortium for Research into Familial Breast Cancer (KConFab) was established four years ago to co-ordinate the collection of genetic, epidemiological and clinical data in Australian families with a dominantly inherited predisposition to breast cancer. The systematic recruitment of large numbers of high risk women by KConFab provides a unique and temporary opportunity to address questions concerning psychosocial predictors of disease development in a prospective design with sufficient power, due to the higher rates of breast and ovarian cancer events in this population. We will also be able to explore interactions with genetic mutation status. The study will be a world first, and provide the most rigorous data to date in this area. If this study demonstrates a relationship between psychosocial factors and the development of breast cancer in women from high risk families, subsequent identification of vulnerable individuals and the implementation of appropriate interventions may have a real impact on reducing morbidity and mortality in this population. Furthermore, the results may have implications for all women in reducing breast cancer incidence.Read moreRead less