David Brewster

Bio: David Brewster is an academic researcher from Flinders University. The author has contributed to research in topics: Public health & Population. The author has an hindex of 23, co-authored 42 publications receiving 2076 citations. Previous affiliations of David Brewster include Fiji School of Medicine & James Cook University.

Skin infection, housing and social circumstances in children living in remote Indigenous communities: testing conceptual and methodological approaches

Abstract: Poor housing conditions in remote Indigenous communities in Australia are a major underlying factor in poor child health, including high rates of skin infections. The aim of this study is to test approaches to data collection, analysis and feedback for a follow-up study of the impact of housing conditions on child health. Participation was negotiated in three communities with community councils and individual participants. Data were collected by survey of dwelling condition, interviews, and audit health centre records of children aged under seven years. Community feedback comprised immediate report of items requiring urgent repair followed by a summary descriptive report. Multivariate models were developed to calculate adjusted incidence rate ratios (IRR) for skin infections and their association with aspects of household infrastructure. There was a high level of participation in all communities. Health centre records were inadequate for audit in one community. The records of 138 children were available for development of multivariate analytic models. Rates of skin infection in dwellings that lacked functioning facilities for removing faeces or which had concrete floors may be up to twice as high as for other dwellings, and the latter association appears to be exacerbated by crowding. Younger children living in older dwellings may also be at approximately two-fold higher risk. A number of socioeconomic and socio-demographic variables also appear to be directly associated with high rates of skin infections. The methods used in the pilot study were generally feasible, and the analytic approach provides meaningful results. The study provides some evidence that new and modern housing is contributing to a reduction in skin infections in Aboriginal children in remote communities, particularly when this housing leads to a reduction in crowding and the effective removal of human waste.

Interethnic genetic differentiation in Africa: HLA class I antigens in The Gambia.

Abstract: A total of 752 individuals from The Gambia, west Africa who are representative of the major ethnic groups in the capital, Banjul, were serologically typed for HLA-A, -B, and -C antigens. Although all were typically "African" in their antigenic profiles, some marked frequency differences were found between the ethnic groups. Genetic distance comparisons with several other African populations showed that, although these west African populations clustered closely together, the positions of the various ethnic groups in The Gambia were consistent with historical and linguistic evidence of their affinities with one another and with other African populations. Despite the potential confounding effects both of selection by infectious diseases and of genetic drift caused by local differences in population structure, HLA frequencies appear to be of value in measuring inter- and intraregional population affinities in sub-Saharan Africa.

Are hygiene and public health interventions likely to improve outcomes for Australian Aboriginal children living in remote communities? A systematic review of the literature

Abstract: Australian Aboriginal children living in remote communities still experience a high burden of common infectious diseases which are generally attributed to poor hygiene and unsanitary living conditions. The objective of this systematic literature review was to examine the epidemiological evidence for a relationship between various hygiene and public health intervention strategies, separately or in combination, and the occurrence of common preventable childhood infectious diseases. The purpose was to determine what intervention/s might most effectively reduce the incidence of skin, diarrhoeal and infectious diseases experienced by children living in remote Indigenous communities. Studies were identified through systematically searching electronic databases and hand searching. Study types were restricted to those included in Cochrane Collaboration Effective Practice and Organisation of Care Review Group (EPOC) guidelines and reviewers assessed the quality of studies and extracted data using the same guidelines. The types of participants eligible were Indigenous populations and populations of developing countries. The types of intervention eligible for inclusion were restricted to those likely to prevent conditions caused by poor personal hygiene and poor living environments. The evidence showed that there is clear and strong evidence of effect of education and handwashing with soap in preventing diarrhoeal disease among children (consistent effect in four studies). In the largest well-designed study, children living in households that received plain soap and encouragement to wash their hands had a 53% lower incidence of diarrhoea (95% CI, 0.35, 0.59). There is some evidence of an effect of education and other hygiene behaviour change interventions (six studies), as well as the provision of water supply, sanitation and hygiene education (two studies) on reducing rates of diarrhoeal disease. The size of these effects is small and the quality of the studies generally poor. Research which measures the effectiveness of hygiene interventions is complex and difficult to implement. Multifaceted interventions (which target handwashing with soap and include water, sanitation and hygiene promotion) are likely to provide the greatest opportunity to improve child health outcomes in remote Indigenous communities.

Exploring cross-sectional associations between common childhood illness, housing and social conditions in remote Australian Aboriginal communities

Abstract: There is limited epidemiological research that provides insight into the complex web of causative and moderating factors that links housing conditions to a variety of poor health outcomes. This study explores the relationship between housing conditions (with a primary focus on the functional state of infrastructure) and common childhood illness in remote Australian Aboriginal communities for the purpose of informing development of housing interventions to improve child health. Hierarchical multi-level analysis of association between carer report of common childhood illnesses and functional and hygienic state of housing infrastructure, socio-economic, psychosocial and health related behaviours using baseline survey data from a housing intervention study. Multivariate analysis showed a strong independent association between report of respiratory infection and overall functional condition of the house (Odds Ratio (OR) 3.00; 95%CI 1.36-6.63), but no significant association between report of other illnesses and the overall functional condition or the functional condition of infrastructure required for specific healthy living practices. Associations between report of child illness and secondary explanatory variables which showed an OR of 2 or more included: for skin infection - evidence of poor temperature control in the house (OR 3.25; 95%CI 1.06-9.94), evidence of pests and vermin in the house (OR 2.88; 95%CI 1.25-6.60); for respiratory infection - breastfeeding in infancy (OR 0.27; 95%CI 0.14-0.49); for diarrhoea/vomiting - hygienic state of food preparation and storage areas (OR 2.10; 95%CI 1.10-4.00); for ear infection - child care attendance (OR 2.25; 95%CI 1.26-3.99). These findings add to other evidence that building programs need to be supported by a range of other social and behavioural interventions for potential health gains to be more fully realised.

Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation

Abstract: Tumor necrosis factor α (TNFα) is a potent immunomodulator and proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. For example, plasma levels of TNFα are positively correlated with severity and mortality in malaria and leishmaniasis. We have previously described a polymorphism at −308 in the TNFα promoter and shown that the rare allele, TNF2, lies on the extended haplotype HLA-A1-B8-DR3-DQ2, which is associated with autoimmunity and high TNFα production. Homozygosity for TNF2 carries a sevenfold increased risk of death from cerebral malaria. Here we demonstrate, with reporter genes under the control of the two allelic TNF promoters, that TNF2 is a much stronger transcriptional activator than the common allele (TNF1) in a human B cell line. Footprint analysis using DNase I and B cell nuclear extract showed the generation of a hypersensitive site at −308 and an adjacent area of protection. There was no difference in affinity of the DNA-binding protein(s) between the two alleles. These results show that this polymorphism has direct effects on TNFα gene regulation and may be responsible for the association of TNF2 with high TNFα phenotype and more severe disease in infections such as malaria and leishmaniasis.

TNF‐mediated inflammatory disease

Abstract: TNF was originally described as a circulating factor that can cause necrosis of tumours, but has since been identified as a key regulator of the inflammatory response This review describes the known signalling pathways and cell biological effects of TNF, and our understanding of the role of TNF in human disease TNF interacts with two different receptors, designated TNFR1 and TNFR2, which are differentially expressed on cells and tissues and initiate both distinct and overlapping signal transduction pathways These diverse signalling cascades lead to a range of cellular responses, which include cell death, survival, differentiation, proliferation and migration Vascular endothelial cells respond to TNF by undergoing a number of pro-inflammatory changes, which increase leukocyte adhesion, transendothelial migration and vascular leak and promote thrombosis The central role of TNF in inflammation has been demonstrated by the ability of agents that block the action of TNF to treat a range of inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease and psoriasis The increased incidence of infection in patients receiving anti-TNF treatment has highlighted the physiological role of TNF in infectious diseases

Common West African HLA antigens are associated with protection from severe malaria

Abstract: A large case-control study of malaria in West African children shows that a human leucocyte class I antigen (HLA-Bw53) and an HLA class II haplotype (DRB1*1302-DQB1*0501), common in West Africans but rare in other racial groups, are independently associated with protection from severe malaria. In this population they account for as great a reduction in disease incidence as the sickle-cell haemoglobin variant. These data support the hypothesis that the extraordinary polymorphism of major histocompatibility complex genes has evolved primarily through natural selection by infectious pathogens.

Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria.

Abstract: Tumour-necrosis factor-alpha (TNF-alpha) is believed to have an important role in the pathogenesis of severe infectious disease and fatal cerebral malaria is associated with high circulating levels of this cytokine. In a large case-control study in Gambian children we find that homozygotes for the TNF2 allele, a variant of the TNF-alpha gene promoter region, have a relative risk of 7 for death or severe neurological sequelae due to cerebral malaria. Although the TNF2 allele is in linkage disequilibrium with several neighbouring HLA alleles, we show that this disease association is independent of HLA class I and class II variation. These data suggest that regulatory polymorphisms of cytokine genes can affect the outcome of severe infection. The maintenance of the TNF2 allele at a gene frequency of 0.16 in The Gambia implies that the increased risk of cerebral malaria in homozygotes is counterbalanced by some biological advantage.