Diseases caused by the pneumococcus represent the largest cause of vaccine preventable death in the world today, mainly pneumonia and meningitis. In 2011, 16 developing countries will introduce pneumococcal conjugate vaccines, none in east Asia. Lack of research has been a major barrier to their use in the region. We have established an international centre of excellence in the field and we seek support to extend the capacity of this group and to transfer the technology to Vietnam.
Understanding The Role Of The Two Major Bacterial Pathogens In The Upper And Lower Airways Of Indigenous Children With Chronic Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$743,282.00
Summary
Lung infections are a major disease burden worldwide. Indigenous Australians are affected more; adults with severe lung disease can die in their 30s and 40s. These diseases start early, yet no in-depth studies of bacteria causing lung infections in children have been done. Our expert team proposes to use existing lung fluids from nearly 500 children with chronic lung disease (58% Indigenous), and state-of-the-art laboratory methods, to inform the design of vaccines to prevent lung disease.
A New Model For The Pathogenesis Of Rheumatic Fever: Superantigen Priming Of The Immune Response To Group A Streptococci
Funder
National Health and Medical Research Council
Funding Amount
$248,820.00
Summary
Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, c ....Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, control of this ARF will partly depend on new and better treatment and prevention strategies. To achieve these goals a deeper understanding of the immune mechanisms underlying this disease is urgently needed. It is known that ARF is caused by an abnormal immune response following streptococcal infection. This leads to the production of cells called T cells that attack the body s own tissues rather than the bacteria itself. This autoimmune disease is responsible for the heart damage that underlies ARF. It is believed that this proces only occurs when susceptible individuals are infected with specific rheumatogenic strains of streptococci. However there are a number of deficiencies in this model and it is proposed that there is an additional factor responsible for the abnormal immune response in ARF. This project will explore the possibility that bacterial toxins called superantigens are the critical missing factor , by studying the immune response in ARF. Superantigens are produced by certain streptococci and staphylococci, and are potent in minute quantities causing widespread activation of the immune system. They have been found to play an important role in a number of autoimmune diseases and the type of immune response found in ARF fits well with that expected if superantigens were involved. If superantigens play an important role in causing the abnormal immune response in ARF then a number of new avenues would open for the treatment and prevention of this disease.Read moreRead less
A Randomised Placebo-controlled Trial Of Antibiotics To Prevent Urinary Tract Infection In Children
Funder
National Health and Medical Research Council
Funding Amount
$735,000.00
Summary
This study is needed to determine whether a common clinical practice long-term antibiotic treatment for children following urinary tract infection (UTI) - is safe and effective in preventing further UTI and if so, whether all appropriate children are being treated. UTI will affect about 10% of Australian children by high school age (88,000 children per year). Because UTI may damage the kidneys, the management priority for children with UTI has been prevention of further infection. Currently this ....This study is needed to determine whether a common clinical practice long-term antibiotic treatment for children following urinary tract infection (UTI) - is safe and effective in preventing further UTI and if so, whether all appropriate children are being treated. UTI will affect about 10% of Australian children by high school age (88,000 children per year). Because UTI may damage the kidneys, the management priority for children with UTI has been prevention of further infection. Currently this means the identification of children thought to be most at risk of recurrent UTI by renal tract imaging. Those found to have reflux of urine from the bladder to the kidney (present in about 30% of those with UTI) are then placed on antibiotics fro 2-5 years. Unfortunately there has never been a properly designed trial to test whether antibiotics do really prevent UTI and if so, whether children with reflux are the appropriate and only group requiring treatment. Long term antibiotics may in fact do more harm than good because of side effects like skin, bowel and blood problems and because resistant bacteria may develop. The design of this study involves the random allocation of placebo or antibiotic (cotrimoxazole, the usual antibiotic given in this case) to about 800 children after their first symptomatic UTI. These children are treated and followed for one year to determine the rate of futher UTI in both groups. Any difference in outcome between the two groups of children will be because of the antibiotic treatment. This study may prove long-term antibiotics are ineffective and therefore should not be routinely used. In this case investigation of children to detect vesicoureteric reflux would serve little purpose and should be abandoned. Alternatively antibiotic treatment may be shown as effective treatment for preventing further UTI and in this case the study will clearly identify those children who will benefit.Read moreRead less
Mathematical Modelling Of Bacterial Carriage In Children
Funder
National Health and Medical Research Council
Funding Amount
$421,746.00
Summary
Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, child ....Children exposed to larger numbers of other children are at risk of persistent bacterial infections. Such circumstances explain the high rates of ear and chest infections, and skin sores seen in children in historical times. Changing social circumstances (smaller families, better housing, nutrition and hygiene), as well as the introduction of antibiotics, explain the decline of such infections in affluent communities since the early 20th century. However, even today, in affluent countries, children attending group child care are at high risk of ear infections. As many bacteria are resistant, antibiotics are now much less effective than when they were first introduced. Furthermore, there is a continuing load of infection for children in Aboriginal communities, in PNG and other developing countries, causing hearing loss, chronic respiratory problems, and heart disease and renal disease in later life. Using data previously collected from other studies in Indigenous communities and children in child care, mathematical models allow us to ask what if?, and answer important public health questions: 1. What environmental and public health measures can reduce the cycle of cross-infection in child-care and high-risk populations? 2. What coverage rates with pneumococcal vaccine will eliminate the vaccine-specific bacteria from child care centres, from the wider community, and from high risk populations? 3. Will infections with bacteria not covered by vaccine then increase? 4. Will the resistant bacteria tend to disappear if antibiotic use is restricted? 5. Under what circumstances will antibiotics help to control infection? The modelling will promote understanding of the social and health costs of bacterial infection in Aboriginal communities and child care and use educational scenarios to promote uptake of the most cost-effective and socially acceptable interventions.Read moreRead less
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 Rotavirus Vaccine Effectiveness Against Gastroenteritis Hospitalisation Of Children In The NT
Funder
National Health and Medical Research Council
Funding Amount
$465,859.00
Summary
Almost 1 out of 5 children in remote Aboriginal communities are hospitalised with diarrhoea caused by rotavirus. This study will evaluate the impact of rotavirus vaccination in preventing these hospitalisations. In addition to making sure that vaccination works and that those at highest risk are receiving the benefits, it will assess the indirect impact against other causes of diarrhoea providing, critical information relevant to the vaccine's broader introduction in developing country settings.
Impact Of DTP Schedules On The Immunogenicity Of 2 Doses Of 13v-PCV Followed By An Early Booster
Funder
National Health and Medical Research Council
Funding Amount
$2,651,687.00
Summary
This project aims to come up with a vaccination schedule to make pneumococcal vaccines more effective and affordable for Fiji and other developing countries. We will evaluate schedules involving a 2 dose primary series in early infancy with a booster at 9 months of age. We will compare the immune responses to 3 different primary series and 2 booster options. The results of this project will be used to provide advice, at global and country levels, regarding introduction of pneumococcal vaccines.