Community-based Surveillance Of Bacterial Respiratory Pathogens In The NT And WA
Funder
National Health and Medical Research Council
Funding Amount
$782,905.00
Summary
This surveillance project is a continuation of previous work that describes the strains of respiratory bacterial pathogens in the various community groups - Indigenous and non-Indigenous - across the NT and in WA (urban and remote areas). New vaccines are complex and whilst overall benefits are considerable, there are potential influences on microbiology that may be unwanted. Detailed knowledge of these effects will assist in selection of the best vaccines for use in Australia.
The pneumococcus is a major cause of bacterial pneumonia, sepsis and meningitis especially in children and the elderly. Antibiotic-resistant pneumococci are becoming more prevalent, and available vaccines have major shortcomings. We propose to identify and characterise the factors produced by this organism during infection that enable it to cause invasive disease. Such factors could be incorporated into protein-based pneumococcal vaccines currently under development.
GENETIC ANALYSIS OF POLYSACCHARIDE CAPSULE BIOSYNTHESIS AND REGULATION IN STREPTOCOCCUS PNEUMONIAE
Funder
National Health and Medical Research Council
Funding Amount
$377,036.00
Summary
Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until r ....Streptococcus pneumoniae (the pneumococcus) is an important cause of invasive diseases such as pneumonia, meningitis and bacteraemia in humans. Many people carry this organism in the nasopharynx asymptomatically. However, in a small proportion, the organism overcomes host defences and invades the body causing life-threatening disease. An essential virulence factor of the pneumococcus is the polysaccharide capsule which protects it from the immune defences of the host during an infection. Until recently, very little was known of the pneumococcal genes involved in production of this antigen. This project aims to continue characterization of these genes, and examination of the factors which regulate their expression. This regulatory mechanism may be very important, because production of increased levels of the polysaccharide capsule is believed to be an crucial step in the transition from carriage to invasion. An understanding of the molecular events involved in biosynthesis and regulation of capsule production will improve our understanding of the disease process and identify alternative targets for antimicrobial therapy.Read moreRead less
Translating Bacterial Molecular Epidemiology Into Information To Improve Infectious Disease Risk Assessment And Control
Funder
National Health and Medical Research Council
Funding Amount
$494,500.00
Summary
Streptococcus pneumoniae (pneumococcus) and group B streptococcus (GBS) are important pathogenic bacteria, which cause septicaemia and meningitis in young infants, the elderly and people with certain chronic diseases. Both consist of a number of different types, some of which are more likely to cause disease than others. Pneumococcal vaccines that protect against the commonest pathogenic types are used in Australia in people most at risk.Antibiotic resistance is an increasing problem, which shou ....Streptococcus pneumoniae (pneumococcus) and group B streptococcus (GBS) are important pathogenic bacteria, which cause septicaemia and meningitis in young infants, the elderly and people with certain chronic diseases. Both consist of a number of different types, some of which are more likely to cause disease than others. Pneumococcal vaccines that protect against the commonest pathogenic types are used in Australia in people most at risk.Antibiotic resistance is an increasing problem, which should be partly off-set by immunisation. Giving antibiotics during labour, to women colonised with GBS, can reduce infection rates in newborns, but there are many disadvantages of this approach, including the risk of increased antibiotic resistance. Vaccines against GBS are mpt yet available. We have developed methods to identify detailed fingerprints of these bacteria which allow us to identify types, antibiotic resistance and, for GBS, other characteristics which can distinguish highly pathogenic strains from the majority that are carried harmlessly and unlikely to cause disease. The methods are still quite slow and expensive and produce complex patterns,which are difficult to interpret rapidly. We plan to develop a new, rapid and relatively inexpensive, fingerprinting system for these bacteria and computer programs to analyse and interpret the results. They will allow us to check the strains of pneumococci that cause disease to make sure that new ones, not covered by the vaccine, do not become more common and reduce the effectiveness of vaccine and that antibiotic resistance does not increase further. The methods will also allow us to study differences between the small proportion of GBS strains that cause neonatal infection and the majority that are carried harmlessly by pregnant women and are of little risk to their babies. Eventually this should allow doctors to identify women whose babies are most at risk, reduce unnecessary antibiotic use.Read moreRead less
The Immunogenicity Of 7-valent Pneumococcal Conjugate Vaccine In Sick Elderly People For Whom Vaccine Is Not Registered
Funder
National Health and Medical Research Council
Funding Amount
$443,800.00
Summary
The bacteria pneumococcus (also known as streptococcus pneumoniae) is the most common cause of pneumonia in the community, and a major cause of illness and death in the elderly. Rates of antibiotic resistance are also increasing. The pneumococcus is a complex bacteria, with over 80 known serotypes. Most human disease in Australia is caused by 23 of these serotypes. Australia has an ageing population. The health and wellbeing of the elderly has been identified as a national priority. Vaccination ....The bacteria pneumococcus (also known as streptococcus pneumoniae) is the most common cause of pneumonia in the community, and a major cause of illness and death in the elderly. Rates of antibiotic resistance are also increasing. The pneumococcus is a complex bacteria, with over 80 known serotypes. Most human disease in Australia is caused by 23 of these serotypes. Australia has an ageing population. The health and wellbeing of the elderly has been identified as a national priority. Vaccination and prevention of serious infections, a common cause of illness in the elderly, is an achievable public health goal. The National Health and Medical Research Council (NHMRC) of Australia recommends that adults aged 65 years and over should be immunised with 23-valent polysaccharide pneumococcal vaccine (PPV). PPV has been available long term in Australia, but the dilemma associated with its use is that it is least effective in those at greatest risk of pneumococcal disease and its complications, the sick elderly population. A new 7-valent pneumococcal conjugate vaccine (PCV-7) has been available since the end of 2000, but is currently indicated only for children, because it has never been tested in adults. This vaccine uses different technology, and is conjugated to a protein to make it more effective. Clinicals trials of PCV7 have largely been limited to children aged 0-4 years, and have shown it protects 93.9% of children under 2 years of age against invasive pneumococcal disease (IPD). Our study aims to look at the efficacy of this new vaccine, currently only registered for children, in the sub-group of the population who are at highest risk for pneumococcal disease - hospitalised elderly. We will vaccinate hospitalised elderly people with PCV or PPV and compare their immune response to the two different vaccines. If PCV is more effective than PPV, this has implications for the development and use of conjuagated pneumococcal vaccines for adults.Read moreRead less
Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, which is responsible for the deaths of millions of children each year in developing countries. The high morbidity and mortality associated with pneumococcal disease is also being exacerbated by the rate at which this organism is acquiring resistance to multiple antibiotics. Existing pneumococcal polysaccharide vaccines are poorly immunogenic in young children and only provide cover against a limited range of serotypes. S ....Streptococcus pneumoniae (the pneumococcus) is an important human pathogen, which is responsible for the deaths of millions of children each year in developing countries. The high morbidity and mortality associated with pneumococcal disease is also being exacerbated by the rate at which this organism is acquiring resistance to multiple antibiotics. Existing pneumococcal polysaccharide vaccines are poorly immunogenic in young children and only provide cover against a limited range of serotypes. Serotype coverage is even lower in the more immunogenic conjugate vaccines currently being developed; these will also be very expensive, thereby limiting their use in developing countries, where the need for effective paediatric vaccines is greatest. Pneumococci produce a variety of proteins which are important in causing disease, but the relative contribution of these factors at each stage of the infection process remain to be determined. Moreover, virtually nothing is known of the mechanism whereby these virulence factors are regulated in response to the external environment of the bacterium. In view of this, we are conducting a comprehensive examination of the mechanisms of pathogenesis of pneumococcal disease, with particular reference to the role of putative virulence proteins. This information is being used to develop cheap and effective vaccines based on pneumococcal protein antigens common to all serotypes.Read moreRead less
Immunogenicity Of 23-valent Pneumococcal Polysaccharide Vaccination Among Indigenous Australian Adolescents And Adults
Funder
National Health and Medical Research Council
Funding Amount
$674,738.00
Summary
Multiple doses of pneumococcal vaccine are recommended for Indigenous Australians under a unique schedule aimed at reducing high rates of pneumococcal disease. However, disease rates have not reduced after several years of the program. This study examines a key, previously unstudied explanation for the lack of disease reduction in this population: that repeated vaccination could produce suboptimal protection against disease. It will provide evidence to underpin future vaccination policy.
Immunising Aboriginal Mothers With Pneumococcal Polysaccharide Vaccine To Prevent Infant Ear Disease And Carriage
Funder
National Health and Medical Research Council
Funding Amount
$1,131,530.00
Summary
Aboriginal children experience the highest rates of acute and chronic ear infections in the world, with resultant permanent ear damage, hearing loss and educational disadvantage. These infections are mainly bacterial, and Streptococcus pneumoniae (pneumococcus) is the predominant pathogen. Pneumococcal colonisation and infection begins within days of birth, many months before any potential immunological protection from infant pneumococcal conjugate vaccine may be expected. New strategies are nee ....Aboriginal children experience the highest rates of acute and chronic ear infections in the world, with resultant permanent ear damage, hearing loss and educational disadvantage. These infections are mainly bacterial, and Streptococcus pneumoniae (pneumococcus) is the predominant pathogen. Pneumococcal colonisation and infection begins within days of birth, many months before any potential immunological protection from infant pneumococcal conjugate vaccine may be expected. New strategies are needed to eliminate, or at least delay, this early-onset pneumococcal colonisation. One such strategy is the administration to the mother of pneumococcal vaccine, which may protect the newborn infant by leading to higher titres of transplacental or breast milk pneumococcal antibodies and-or by reducing carriage (and transmission to the infant) of maternal pneumococci. Previous small studies using this strategy have been encouraging, but there have been no studies properly evaluating carriage or disease endpoints in infants. The polysaccharide pneumococcal vaccine is currently recommended for all Aboriginal and Torres Islander persons aged 15 years or more in the Northern Territory but uptake of the vaccine has been poor. We propose to conduct a pilot study to determine if maternal immunisation with this vaccine, either in the third trimester of pregancy of immediately following delivery, can reduce pneumococcal carriage and the prevalence of middle ear disease among Aboriginal infants at seven months of age. We aim to recruit 210 Aboriginal women who have uncomplicated pregnancies from Darwin and remote communities in the Top End of the Northern Territory. Each subject and their infant offspring will be followed-up after vaccination and at birth, one , two and seven months after birth.Read moreRead less
PneuMum: An RCT Of Maternal Pneumococcal Vaccination For Protection Of Indigenous Children From Ear Disease
Funder
National Health and Medical Research Council
Funding Amount
$591,291.00
Summary
Ear disease starts in the first few months of life for most Indigenous children. By school entry, 2 out of every 3 Indigenous children in the NT have hearing problems. This proposal is to renew funding of the PneuMum study, which aims to find out whether the protection that a mother gets when she receives a pneumococcal vaccine late in pregnancy or soon after delivery can help to protect her child from getting ear disease.
Improved Hygiene Measures For Australian Child Care Centres: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$440,573.00
Summary
Roughly fifty percent of young Australian children receive care outside their home. As greater numbers of women choose to continue working after childbirth, the proportion of children exposed to group care in the first few years of life will continue to increase. In developed countries child care attendance has been shown to be the most important modifiable risk factor for respiratory tract infections and otitis media. A previous study in nine Darwin child care centres demonstrated high rates of ....Roughly fifty percent of young Australian children receive care outside their home. As greater numbers of women choose to continue working after childbirth, the proportion of children exposed to group care in the first few years of life will continue to increase. In developed countries child care attendance has been shown to be the most important modifiable risk factor for respiratory tract infections and otitis media. A previous study in nine Darwin child care centres demonstrated high rates of respiratory tract infections, otitis media, antibiotic use and colonisation with both penicillin-sensitive and penicillin-resistant pneumococci. This study will assess the impact of simple hygiene measures on rates of pneumococcal colonisation, respiratory infection, otitis media, and pneumococcal antibiotic resistance. Twenty child care centres will be randomised to receive additional training and education in the prevention of spread of respiratory infection or routine care. Outcomes measures will include the number of new infection with Streptococcus pneumoniae and Haemophilus influenzae, reported illnesses, and rates of otitis media and nasal discharge documented by fortnightly examination with video recording and tympanometry. Efficacy of the intervention will be estimated at the end of the school year (9 months after the intervention) to avoid bias associated with changes in the child care environment that occur over the school holidays. The centres randomised to routine care will receive the full intervention at the completion of the study and all centres will be re-assessed 6 months .Read moreRead less