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Biomedical subjects

B J Currie

Publications and source records attributed to B J Currie.

At least 19 recordsLinked to original sources

Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature.

OBJECTIVES: To describe the clinical and immunological features of crusted scabies in a prospectively ascertained cohort of 78 patients. METHODS: All patients requiring inpatient treatment for crusted scabies in the 'top end' of the northern territory of Australia over a 10 year period were prospectively identified. Demographics, risk factors, and immunological parameters were retrospectively compiled from their medical records and pathology databases. RESULTS: More than half the patients with crusted scabies had identifiable immunosuppressive risk factors. Eosinophilia and elevated IgE levels occurred in 58% and 96% of patients, respectively, with median IgE levels 17 times the upper limit of normal. Seventeen percent had a history of leprosy but 42% had no identifiable risk factors. There was a decrease in mortality after the introduction of a treatment protocol consisting of multiple doses of ivermectin combined with topical scabicides and keratolytic therapy. CONCLUSIONS: Crusted scabies often occurs in patients with identifiable immunosuppressive risk factors. In patients without such risk factors, it is possible that the crusted response to infection results from a tendency to preferentially mount a Th2 response. The treatment regime described was associated with a reduction in mortality. This is the largest reported case series of crusted scabies.

Administration, Oral↗

Seroprevalence of Burkholderia pseudomallei in East Timorese refugees: implications for healthcare in East Timor.

Melioidosis is a disease with protean clinical manifestations caused by the bacterium Burkholderia pseudomallei. It is endemic in countries surrounding the newly independent East Timor, but has yet to be isolated or demonstrated serologically in that country. One illness that can be clinically indistinguishable from melioidosis is pulmonary tuberculosis, a condition with a very high prevalence in East Timor. We used an indirect hemagglutination test (IHA) to measure antibodies to B. pseudomallei in 407 East Timorese evacuated to Darwin, Australia, in September 1999. Assuming a positive IHA titer as > or = 1:40, the overall seroprevalence rate was 17.0%, in keeping with other seroprevalence studies from the region. The IHA titres ranged up to 1:320. After adjusting for age, females were 2.5 times more likely to be seropositive than males (p = 0.0001). There was an inverse relationship between seropositivity and age. This study shows that exposure to B. pseudomallei occurs in East Timor melioidosis is also likely to occur. Due to the lack of laboratory facilities at present, it may be some time before a laboratory-confirmed case proves that melioidosis occurs. In the meantime, clinicians in East Timor should include melioidosis in the differential diagnosis of the many conditions that it may mimic.

Adolescent↗

Trachipleistophora hominis infection in the myocardium and skeletal muscle of a patient with AIDS.

OBJECTIVES: To review the literature relevant to microsporidial infection of muscle and to describe a case of human microsporidial infection involving both skeletal and cardiac muscle. METHODS: Samples from an AIDS patient with myositis have been examined by light and electron microscopy. RESULTS: We describe the findings at autopsy of a 47 year old Australian male with late stage AIDS, who had skeletal and cardiac muscle involvement with the microsporidian Trachipleistophora hominis. This is the third definitively identified case of human T. hominis infection and the first to describe infection of the myocardium. CONCLUSIONS: Microsporidial infection of muscle is rare in humans, but more work is needed to elucidate both the organisms and routes of transmission of this group of parasitic protozoa.

AIDS-Related Opportunistic Infections↗

Analysis of Sarcoptes scabiei finds no evidence of infection with Wolbachia.

The endosymbiont Wolbachia has been detected in a range of filarial nematodes and parasitic mites and is known to affect host reproductive compatibility and potentially evolutionary processes. PCR of Wolbachia surface protein (wsp), ftsZ and 16SrRNA genes from individual Sarcoptes scabiei mites obtained from a series of individual hosts, and database searches of an S. scabiei var. hominis EST library failed to detect Wolbachia genes. Therefore, Wolbachia appears not to be involved in the genetic subdivision observed between varieties of host-associated S. scabiei or, involved in the inflammatory disease pathogenesis of scabies unlike its activity in filarial infection.

Animals↗

Granulocyte colony-stimulating factor and an in vitro whole blood model of melioidosis.

The study reported here was conducted in order to explore the mechanism of action of granulocyte colony-stimulating factor (G-CSF) in the treatment of Burkholderia pseudomallei infections (otherwise known as melioidosis). Use of G-CSF as an adjunct to antibiotics has been associated with decreasing mortality among patients with melioidosis in the tropical region of the Northern Territory of Australia. However, using an in vitro whole blood assay, no significant difference was detected in the bactericidal activity of samples obtained from dialysis patients, patients with type 2 diabetes mellitus and healthy controls, and there was no improvement following coincubation with G-CSF.

Australia↗

Granulocyte-Colony Stimulating Factor (G-CSF) as an adjunct to antibiotics in the treatment of pneumonia in adults.

BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropaenia, but its role in the treatment of infection in non-neutropaenic hosts is less well defined. OBJECTIVES: We explored the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropaenic adults. SEARCH STRATEGY: We searched the following electronic databases in 2003 and updated the search in 2004: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004); MEDLINE (January 1966 to March Week 1, 2004); EMBASE (1998 to December 2003); online databases of clinical trials; and reference lists of articles. We also contacted study authors, manufacturers and distributors of G-CSF. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) which included hospitalised adult patients with either community acquired pneumonia or hospital-acquired pneumonia. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. The primary outcome measure was 28 day mortality. Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction. An assessment of methodological quality was made for each study. MAIN RESULTS: Six studies with a total of 1984 people were identified. G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled odds ratio (OR) 0.91; 95% confidence interval (CI): 0.73 to 1.14) or organ dysfunction. However, the use of G-CSF was not associated with improved 28 day mortality (pooled OR 0.86; 95% CI: 0.56 to 1.31). REVIEWERS' CONCLUSIONS: There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.

Adult↗

Genetic epidemiology of Sarcoptes scabiei (Acari: Sarcoptidae) in northern Australia.

Utilising three hypervariable microsatellite markers we have previously shown that scabies mites on people are genetically distinct from those on dogs in sympatric populations in northern Australia. This had important ramifications on the formulation of public health control policies. In contrast phylogenetic analyses using mitochondrial markers on scabies mites infecting multiple animal hosts elsewhere in the world could not differentiate any genetic variation between mite haplotype and host species. Here we further analyse the intra-specific relationship of Sarcoptes scabiei var. hominis with S. scabiei var. canis by using both mitochondrial DNA and an expanded nuclear microsatellite marker system. Phylogenetic studies using sequences from the mitochondrial genes coding for 16S rRNA and Cytochrome Oxidase subunit I demonstrated significant relationships between S. scabiei MtDNA haplotypes, host species and geographical location. Multi-locus genotyping using 15 microsatellite markers substantiated previous data that gene flow between scabies mite populations on human and dog hosts is extremely rare in northern Australia. These data clearly support our previous contention that control programs for human scabies in endemic areas with sympatric S. scabiei var. hominis and var. canis populations must focus on human-to-human transmission. The genetic division of dog and human derived scabies mites also has important implications in vaccine and diagnostic test development as well as the emergence and monitoring of drug resistance in S. scabiei in northern Australia.

Animals↗

Preliminary report on the northern Australian melioidosis environmental surveillance project.

An environmental surveillance programme was developed to determine whether water supplies could be a source of Burkholderia pseudomallei as noted during previous melioidosis outbreak investigations. Water supplies to communities in the three northern Australian jurisdictions (Western Australia, Northern Territory and Queensland) were sampled periodically during 2001 and 2002. Water and soil samples were collected from communities known to have had recent culture-positive melioidosis cases and nearby communities where no cases had been diagnosed. Clinical isolates of B. pseudomallei obtained from northern Australian patients during 2001 and 2002 were compared with the environmental B. pseudomallei isolates by ribotyping and pulsed-field gel electrophoresis. B. pseudomallei was isolated from 11 distinct locations, all in the Northern Territory, seven of which were associated with culture-positive melioidosis cases (>1 case at three locations). Water was implicated as a possible environmental source of melioidosis in six locations. A variety of free-living amoebae including Acanthamoeba and Hartmannella spp. that are potential hosts to B. pseudomallei were recovered from environmental specimens. Culturable B. pseudomallei was not found to be widely dispersed in the environments sampled.

Animals↗

Comparison of the susceptibilities of Burkholderia pseudomallei to meropenem and ceftazidime by conventional and intracellular methods.

The effect of the two antibiotics ceftazidime and meropenem on a collection of 46 Burkholderia pseudomallei isolates representing clinical and environmental sources across northern Australia was investigated by using a series of in vitro test methods. The susceptibility testing methods used included Kirby-Bauer disk diffusion, Etest MIC, broth microdilution MIC, and a modification of the microdilution method in which Acanthamoeba cells were added to simulate the effect of a professional phagocytic cell on test outcome. In a semiquantitative validation coculture series, the majority of bacteria were intracellular up to a multiplicity of infection of 10 bacteria to one ameba. The optical density and bacterial count (log10 CFU/ml) correlated across the range tested (r2 = 0.77; P < 0.0001). Susceptibility test results were compared against clinical outcomes. The MICs of ceftazidime were consistently higher than those of meropenem by all three methods. The MICs of both agents were significantly higher when Acanthamoeba trophozoites were added to the broth microdilution method. Conventional and intracellular MIC results were consistent for clinical isolates from the Western Australian outbreak cluster despite the wide variety of clinical outcomes. Further development of the intracellular MIC method is expected to help assess the efficacy of antimicrobial agents on this bacterial species in an intracellular setting.

Acanthamoeba↗

Intranasal vaccination with streptococcal fibronectin binding protein Sfb1 fails to prevent growth and dissemination of Streptococcus pyogenes in a murine skin infection model.

Fibronectin binding protein F1 (Sfb1) of Streptococcus pyogenes (group A streptococcus [GAS]) is a well-characterized adhesin that has been shown to induce protection in mice against a lethal intranasal GAS challenge after intranasal immunization with cholera toxin B subunit (CTB) as adjuvant. With a murine skin infection model, we have shown that Sfb1/CTB vaccination neither elicits opsonizing antibodies nor prevents systemic bacterial growth and dissemination to internal organs after a subcutaneous GAS challenge. These results indicate that an Sfb1-based vaccine should be complemented with additional protective antigens in order to be used in areas such as the tropical north of Australia, where the skin is the primary route of entry for invasive streptococcal diseases.

Adhesins, Bacterial↗

Saccade dysfunction associated with chronic petrol sniffing and lead encephalopathy.

BACKGROUND: In chronic petrol sniffers, recent exposure to high levels of leaded petrol may give rise to a lead encephalopathy characterised by tremor, chorea, ataxia, hyperreflexia, convulsive seizures, and death. Neurological abnormalities associated with lead encephalopathy involve the cortex, basal ganglia, cerebellum, and brain stem. OBJECTIVE: To use saccadic eye movement tasks as an experimental tool to determine which CNS changes are associated with chronic petrol sniffing and which with a history of lead encephalopathy, and to what extent these changes are reversible. METHODS: Saccade function was assessed in chronic petrol sniffers with a history of lead encephalopathy (encephalopathic sniffers), chronic petrol sniffers who had never suffered lead encephalopathy (chronic sniffers), individuals who had sniffed petrol in the past but had not done so for more than six months (ex-sniffers), and individuals who had never sniffed petrol (non-sniffers). RESULTS: Chronic sniffers showed increased latency of visually guided saccades and antisaccades and increased antisaccade errors which suggested cortical and basal ganglia dysfunction. These abnormalities returned to normal in ex-sniffers. Encephalopathic sniffers showed the same abnormalities as chronic sniffers but with greater severity and additional saccadic signs including dysmetria, gaze evoked nystagmus, and saccade slowing which usually indicate cerebellar and brain stem dysfunction. CONCLUSIONS: Chronic petrol abuse is associated with cortical and basal ganglia abnormalities that are at least partially recoverable with abstinence. Additional long term cerebellar and brain stem abnormalities are associated with lead encephalopathy.

Adolescent↗

Scabies: more than just an irritation.

Human scabies, caused by skin infestation with the arthropod mite, Sarcoptes scabiei, typically results in a papular, intensely pruritic eruption involving the interdigital spaces, and flexure creases. Recent research has led to a reassessment of the morbidity attributable to this parasite in endemic communities, particularly resulting from secondary skin sepsis and postinfective complications including glomerulonephritis. This has led to studies of the benefits of community based control programmes, and to concerns regarding the emergence of drug resistance when such strategies are employed. The renewed research interest into the biology of this infection has resulted in the application of molecular tools. This has established that canine and human scabies populations are genetically distinct, a finding with major implications for the formulation of public health control policies. Further research is needed to increase understanding of drug resistance, and to identify new drug targets and potential vaccine candidates.

Animal Diseases↗

Immune responses of a liposome/ISCOM vaccine adjuvant against streptococcal fibronectin binding protein 1 (Sfb1) in mice.

BACKGROUND & OBJECTIVES: The fibronectin binding protein Sfb1 of Streptococcus pyogenes is a well characterised antigen which induces protection against lethal challenge with group A streptococcus (GAS) when adjuvanted with cholera toxin B-subunit (CTB). As an alternative to CTB adjuvanted intranasal immunisations we investigated the immune responses generated in mice using Sfb1 incorporated in to the skin and mucosal adjuvant SAMA4. METHODS: Mice (BALB/c) were vaccinated intradermally with 100 microl of either SAMA4 (adjuvant only group) or SAMA4/Sfb1 and were boosted 7 days later. Mice vaccinated with CTB based vaccines were immunised by intranasal inoculation with a mixture containing 30 microg Sfb1 and 10 microg CTB on days 1, 3, 5 and 15. At 14 days after the last booster immunisation the immune response was characterised and mice were challenged with 10(8) CFU of S. pyogenes. RESULTS: Mice vaccinated with SAMA4/Sfb1 elicited a Sfb1-specific IgG response in the sera that was significantly higher than that seen in control mice and mice immunised with the adjuvant only (P<0.05). No significant differences were seen for specific IgA antibodies in the sera in all groups examined. Compared with non-immunised and adjuvant only immunised controls, mice immunised with the Sfb1/SAMA4 vaccine exhibited a significant increase (P<0.05) in the number of Sfb1 reactive spleen cells in lymphoproliferation assays which were three fold higher than those seen for mice vaccinated with the Sfb1/CTB vaccine. Mice vaccinated with CTB/Sfb1 had the highest level of protection (80%) as where mice vaccinated with SAMA4 and SAMA4/Sfb1 displayed no protection (20% and 40%). INTERPRETATION & CONCLUSION: These data suggest that the SAMA4 adjuvant used in this study fails to elicit protective immunity in BALB/c mice when used to adjuvant the known protective antigen Sfb1.

Adhesins, Bacterial↗

Ear drops for the removal of ear wax.

BACKGROUND: Problems attributed to the accumulation of wax (cerumen) are one of the most common reasons for people to present to their general practitioners with ear trouble (Sharp 1990). Treatment for this condition often involves use of a wax softening agent (cerumenolytic) in order to disperse the cerumen and reduce the need for syringing, or to facilitate syringing should it prove necessary, but there is no consensus on the effectiveness of the wide variety of cerumenolytics in use. OBJECTIVES: To assess the effectiveness of ear drops (cerumenolytics) for the removal of symptomatic ear wax. SEARCH STRATEGY: We searched the Cochrane ENT Group Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2003), and MEDLINE and EMBASE up to March 2003. Reference lists of all trials were also manually searched. SELECTION CRITERIA: We identified all randomised controlled trials (with or without blinding) in which a cerumenolytic was evaluated in comparison with either no treatment, a placebo, or other cerumenolytics in participants with hard or impacted ear wax, and in which the proportion of participants with sufficient clearance of the external canal to make further mechanical clearance unnecessary (primary outcome measure) was stated or calculable. The full text articles of all the retrieved trials of possible relevance were reviewed by the two reviewers and the inclusion criteria applied independently. Any differences in opinion about which studies to include in the review were resolved by discussion. DATA COLLECTION AND ANALYSIS: Trials were graded for methodological quality using the Cochrane approach. Data extraction was performed in a standardised manner by one reviewer and rechecked by the other reviewer, and where necessary investigators were contacted to obtain missing information. Meta-analysis was neither possible nor considered appropriate because of the heterogeneity of the treatments, treatment amounts and durations, trial procedures, and scoring systems. A narrative overview of the results is therefore presented. MAIN RESULTS: Eight trials satisfied the inclusion criteria, the majority of which were of poor quality. In all, 587 participants received one of nine different cerumenolytics. One trial compared active treatments with no treatment, two trials compared active treatments with water or a saline 'placebo', and all eight trials placed two or more active treatments in head-to-head comparisons. Seven trials included syringing as a secondary treatment where necessary.Overall, results were inconclusive. One trial found a significant difference between one of three active agents (Cerumol) in comparison to no treatment, but no statistically significant difference was found between these three agents (sodium bicarbonate ear drops; Cerumol; sterile water). In two trials no statistical difference was found between the effectiveness of either sodium bicarbonate ear drops, Cerumol, Cerumenex or Colace versus a sterile water or saline 'placebo'. Three trials (from the same source) found statistically significant differences in favour of the same active agent (Exterol) in comparison to glycerol and Cerumol. Three trials found no statistically significant difference between two or more cerumenolytics (Otocerol versus Cerumol; Audax versus Earex; sodium bicarbonate ear drops versus Cerumol). Two trials comparing the same two cerumenolytics (Cerumenex versus Colace) also failed to show any significant benefit of one over the other. No serious adverse effects were reported from any of the interventions. REVIEWER'S CONCLUSIONS: Trials to date have been heterogeneous and of poor quality, making it difficult to offer any definitive recommendations on the effectiveness of cerumenolytics for the removal of symptomatic ear wax. Future trials should be of high methodological quality, have large sample sizes, and compare both oil-based and water-based solvents with placebo and/or no treatment.

Carbamide Peroxide↗

Case-control study of the association between kava use and pneumonia in eastern Arnhem and Aboriginal communities (Northern Territory, Australia).

Pneumonia causes significant morbidity and mortality in Aboriginal populations in Australia's Northern Territory (NT). Kava, consumed in Arnhem Land since 1982, may be a risk factor for infectious disease including pneumonia. A case-control study (n = 115 cases; n = 415 controls) was conducted in 7001 Aboriginal people (4217 over 15 years). Odds ratios (OR) were calculated by conditional logistic regression with substance use and social factors as confounders. Pneumonia was not associated with kava use. Crude OR = 1.26 (0.74-2.14, P = 0.386), increased after controlling for confounders (OR = 1.98, 0.63-6.23, P = 0.237) but was not significant. Adjusted OR for pneumonia cases involving kava and alcohol users was 1.19 (0.39-3.62, P = 0.756). In communities with longer kava-using histories, adjusted OR was 2.19 (0.67-7.14, P = 0.187). There was no kava dose-response relationship. Crude ORs for associations between pneumonia and cannabis use (OR = 2.27, 1 18-4.37, P = 0.014) and alcohol use (OR = 1.95, 1.07-3.53, P = 0.026) were statistically significant and approached significance for petrol sniffing (OR = 1.98, 0.99-3.95, P = 0.056).

Adult↗

Health effects of kava use in an eastern Arnhem Land Aboriginal community.

BACKGROUND: Heavy kava use in Aboriginal communities has been linked to various health effects, including anecdotes of sudden cardiac deaths. AIMS: To examine associations between kava use and potential health effects. METHODS: A cross-sectional study was carried out within a kava-using east Arnhem Land Aboriginal community in tropical northern Australia. One-hundred-and-one adults who were current, recent or non-users of kava were enrolled in March 2000. Main outcome measures were physical, anthropometric, biochemical, haematological, immunological and neurocognitive assessments. RESULTS: Kava users more frequently showed a characteristic dermopathy (P<0.001). They had increased levels of gamma-glutamyl transferase and alkaline phosphatase (P<0.001). Lymphocyte counts were significantly lower in kava users (P<0.001). Fibrinogen, plasminogen activator inhibitor-1 and neurocognitive tests were not different between kava use categories. IgE and IgG antibodies were elevated across the whole group, as were C-reactive protein and homocysteine. CONCLUSIONS: Kava use was associated with dermopathy, liver function abnormalities and decreased lymphocytes. If kava continues to be used by Aboriginal populations, monitoring should focus on the health consequences of these findings, including a possible increase in serious infections. The interaction between kava, alcohol and other substances requires further study. Although markers of cardiovascular risk are increased across the population, these were not higher in kava users, and this increase may be linked to the large infectious pathogen burden reflective of the socioeconomic disadvantage seen in many remote Aboriginal communities.

Adult↗