Rheumatic chorea in northern Australia: a clinical and epidemiological study.
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To describe the epidemiology and clinical features of Sydenham's chorea in the Aboriginal population of northern Australia a review was conducted of 158 episodes in 108 people: 106 were Aborigines, 79 were female, and the mean age was 10.9 years at first episode. Chorea occurred in 28% of cases of acute rheumatic fever, carditis occurred in 25% of episodes of chorea, and arthritis in 8%. Patients with carditis or arthritis tended to have raised acute phase reactants and streptococcal serology. Two episodes lasted at least 30 months. Mean time to first recurrence of chorea was 2.1 years compared with 1.2 years to second recurrence. Established rheumatic heart disease developed in 58% of cases and was more likely in those presenting with acute carditis, although most people who developed rheumatic heart disease did not have evidence of acute carditis with chorea. Differences in the patterns of chorea and other manifestations of acute rheumatic fever in different populations may hold clues to its pathogenesis. Long term adherence to secondary prophylaxis is crucial following all episodes of acute rheumatic fever, including chorea, to prevent recurrence. (+info)
Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism.
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Two of the three class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode known functional variants that act on alcohol with different efficiencies. Variants at both these genes have been implicated in alcoholism in some populations because allele frequencies differ between alcoholics and controls. Specifically, controls have higher frequencies of the variants with higher Vmax (ADH2*2 and ADH3*1). In samples both of alcoholics and of controls from three Taiwanese populations (Chinese, Ami, and Atayal) we found significant pairwise disequilibrium for all comparisons of the two functional polymorphisms and a third, presumably neutral, intronic polymorphism in ADH2. The class I ADH genes all lie within 80 kb on chromosome 4; thus, variants are not inherited independently, and haplotypes must be analyzed when evaluating the risk of alcoholism. In the Taiwanese Chinese we found that, only among those chromosomes containing the ADH3*1 variant (high Vmax), the proportions of chromosomes with ADH2*1 (low Vmax) and those with ADH2*2 (high Vmax) are significantly different between alcoholics and controls (P<10-5). The proportions of chromosomes with ADH3*1 and those with ADH3*2 are not significantly different between alcoholics and controls, on a constant ADH2 background (with ADH2*1, P=.83; with ADH2*2, P=.53). Thus, the observed differences in the frequency of the functional polymorphism at ADH3, between alcoholics and controls, can be accounted for by the disequilibrium with ADH2 in this population. (+info)
Clinical and epidemiological features of group A streptococcal bacteraemia in a region with hyperendemic superficial streptococcal infection.
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Reports of increasing incidence and severity of invasive group A streptococcal (GAS) infections come mainly from affluent populations where exposure to GAS is relatively infrequent. We conducted a 6-year retrospective review of GAS bacteraemia in the Northern Territory of Australia, comparing the Aboriginal population (24% of the study population), who have high rates of other streptococcal infections and sequelae, to the non-Aboriginal population. Of 72 episodes, 44 (61%) were in Aboriginal patients. All 12 cases in children were Aboriginal. Risk factors were implicated in 82% of episodes (91% in adults) and there was no significant difference in the proportion of Aboriginal compared to non-Aboriginal patients with at least one risk factor. Genetic typing of isolates revealed no dominant strains and no evidence of a clone which has been a common cause of these infections elsewhere. (+info)
Proteinuria is associated with persistence of antibody to streptococcal M protein in Aboriginal Australians.
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Aboriginal communities in Northern Australia with high rates of group A streptococcal (GAS) skin infection in childhood also have high rates of renal failure in adult life. In a cross-sectional study of one such high risk community, albuminuria was used as a marker of renal disease. The prevalence of albuminuria increased from 0/52 in subjects aged 10-19 years to 10/29 (32.9%) in those aged 50 or more (P < 0.001). Antibodies to streptococcal M protein, markers of past GAS infection, were present in 48/52 (92%) at ages 10-19 years, 16/32 (50%) at ages 30-39, and 20/29 (69%) in those aged 50 or more. After allowing for the age-dependencies of albuminuria and of M protein antibodies (P < 0.001) albuminuria was significantly associated with M protein antibodies (P < 0.01). Thus, 72% of adults aged 30 or more with M protein antibodies also had albuminuria, compared with only 21% of those who were seronegative. More detailed modelling suggested that although most Aboriginal people in this community developed M protein antibodies following GAS infection in childhood, the development of proteinuria was associated with the persistence of such seropositivity into adult life. The models predicted that proteinuria developed at a mean age of 30 years in seropositive persons, at 45 years in seronegative persons who were overweight, and at 62 years in seronegative persons of normal weight. We demonstrated a clear association between evidence of childhood GAS infection and individual risk of proteinuria in adult life. This study provided a strong rationale for prevention of renal disease through the more effective control of GAS skin infections in childhood and through the prevention of obesity in adult life. (+info)
Pulsed-field gel electrophoresis used to investigate genetic diversity of Haemophilus influenzae type b isolates in Australia shows differences between Aboriginal and non-Aboriginal isolates.
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We used pulsed-field gel electrophoresis to study the epidemiology and population structure of Haemophilus influenzae type b. DNAs from 187 isolates recovered between 1985 and 1993 from Aboriginal children (n = 76), non-Aboriginal children (n = 106), and non-Aboriginal adults (n = 5) in urban and rural regions across Australia were digested with the SmaI restriction endonuclease. Patterns of 13 to 17 well-resolved fragments (size range, approximately 8 to 500 kb) defining 67 restriction fragment length polymorphism (RFLP) types were found. Two types predominated. One type (n = 37) accounted for 35 (46%) of the isolates from Aboriginals and 2 (2%) of the isolates from non-Aboriginals, and the other type (n = 41) accounted for 2 (3%) of the isolates from Aboriginals and 39 (35%) of the isolates from non-Aboriginals. Clustering revealed seven groups at a genetic distance of approximately 50% similarity in a tree-like dendrogram. They included two highly divergent groups representing 50 (66%) isolates from Aboriginals and 6 (5%) isolates from non-Aboriginals and another genetically distinct group representing 7 (9%) isolates from Aboriginals and 81 (73%) isolates from non-Aboriginals. The results showed a heterogeneous clonal population structure, with the isolates of two types accounting for 42% of the sample. There was no association between RFLP type and the diagnosis of meningitis or epiglottitis, age, sex, date of collection, or geographic location, but there was a strong association between the origin of isolates from Aboriginal children and RFLP type F2a and the origin of isolates from non-Aboriginal children and RFLP type A8b. The methodology discriminated well among the isolates (D = 0.91) and will be useful for the monitoring of postvaccine isolates of H. influenzae type b. (+info)
Rheumatic disease and the Australian aborigine.
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OBJECTIVE: To document the frequency and disease phenotype of various rheumatic diseases in the Australian Aborigine. METHODS: A comprehensive review was performed of the archaeological, ethnohistorical, and contemporary literature relating to rheumatic diseases in these indigenous people. RESULTS: No evidence was found to suggest that rheumatoid arthritis (RA), ankylosing spondylitis (AS), or gout occurred in Aborigines before or during the early stages of white settlement of Australia. Part of the explanation for the absence of these disorders in this indigenous group may relate to the scarcity of predisposing genetic elements, for example, shared rheumatoid epitope for RA, B27 antigen for AS. In contrast, osteoarthritis appeared to be common particularly involving the temporomandibular joint, right elbow and knees and, most probably, was related to excessive joint loading in their hunter gatherer lifestyle. Since white settlement, high frequency rates for rheumatic fever, systemic lupus erythematosus, and pyogenic arthritis have been observed and there are now scanty reports of the emergence of RA and gout in these original Australians. CONCLUSION: The occurrence and phenotype of various rheumatic disorders in Australian Aborigines is distinctive but with recent changes in diet, lifestyle, and continuing genetic admixture may be undergoing change. An examination of rheumatic diseases in Australian Aborigines and its changing phenotype may lead to a greater understanding of the aetiopathogenesis of these disorders. (+info)
Indigenous peoples and the morality of the Human Genome Diversity Project.
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In addition to the aim of mapping and sequencing one human's genome, the Human Genome Project also intends to characterise the genetic diversity of the world's peoples. The Human Genome Diversity Project raises political, economic and ethical issues. These intersect clearly when the genomes under study are those of indigenous peoples who are already subject to serious economic, legal and/or social disadvantage and discrimination. The fact that some individuals associated with the project have made dismissive comments about indigenous peoples has confused rather than illuminated the deeper issues involved, as well as causing much antagonism among indigenous peoples. There are more serious ethical issues raised by the project for all geneticists, including those who are sympathetic to the problems of indigenous peoples. With particular attention to the history and attitudes of Australian indigenous peoples, we argue that the Human Genome Diversity Project can only proceed if those who further its objectives simultaneously: respect the cultural beliefs of indigenous peoples; publicly support the efforts of indigenous peoples to achieve respect and equality; express respect by a rigorous understanding of the meaning of equitable negotiation of consent, and ensure that both immediate and long term economic benefits from the research flow back to the groups taking part. (+info)
Functional analysis of IgA antibodies specific for a conserved epitope within the M protein of group A streptococci from Australian Aboriginal endemic communities.
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The mucosa is one of the initial sites of group A streptococcal (GAS) infection and salivary IgA (sIgA) is thought to be critical to immunity. However, the target epitopes of sIgA and the function of sIgA in GAS immunity, in particular the role of accessory cells and complement, is largely unknown. We studied the aquisition and the function of sIgA specific for a conserved region epitope, p145 (sequence: LRRDLDASREAKKQVEKALE) of the M protein. Peptide 145-specific sIgA is highly prevalent within an Aboriginal population living in an area endemic for GAS and acquisition of p145-specific sIgA increases with age, consistent with a role for such antibodies in immunity to GAS. Human sIgA and IgG specific for p145 were affinity purified and shown to opsonize M5 GAS in vitro. Opsonization could be specifically inhibited by the addition of free p145 to the antibodies during assay. Opsonization of GAS was totally dependent on the presence of both complement and polymorphonuclear leukocytes, and, moreover, affinity-purified p145-specific sIgA was shown to fix complement in the presence of M5 GAS. These data show that mucosal IgA to this conserved region peptide within the M protein has an important role in human immunity against GAS and may be useful in a broad-based cross-protective anti-streptococcal vaccine. (+info)