An evaluation of a SAFE-style trachoma control program in central Australia.
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Adolescent↗
Biomedical subjects
Bart J Currie
Publications and source records attributed to Bart J Currie.
Kava hepatotoxicity with Western herbal products: does it occur with traditional kava use?
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Chemical and Drug Induced Liver Injury↗
Saccade and cognitive impairment associated with kava intoxication.
Kava is an extract from the Piper methysticum Forst. f. plant that has social and spiritual importance in Pacific islands societies. Herbal remedies that contain kava are used for the psychiatric treatment of anxiety and insomnia. Laboratory studies have found only subtle, if any, changes on cognitive or motor functions from the acute effects of consuming small clinical doses of kava products. Intoxication from recreational doses of kava has not been studied. The performance of individuals intoxicated from drinking kava (n=11) was compared with a control group (n=17) using saccade and cognitive tests. On average, intoxicated individuals had consumed 205 g of kava powder each (approximately 150 times clinical doses) in a group session that went for 14.4 h and ended 8 h prior to testing. Intoxicated kava drinkers showed ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP), together with saccadic dysmetria, saccadic slowing and reduced accuracy performing a visual search task that only became evident as the task complexity increased. Kava intoxication is characterized by specific abnormalities of movement coordination and visual attention but normal performance of complex cognitive functions. Saccade abnormalities suggest disruption of cerebellar and GABAergic functions.
Adult↗
Saccade and cognitive function in chronic kava users.
Kava is an extract from the Piper methysticum Forst. f. plant that has been consumed in the Pacific islands for millennia and more recently, among indigenous populations, in northern Australia and throughout the Western world as an herbal medicine. Through alterations on neuronal excitation, kava induces muscle relaxation, anasthesia, and has anxiolytic properties. There have been several isolated reports of psychotic syndromes, severe choreoathetosis and possible seizures following kava use. However, there is no conclusive evidence that kava interferes with normal cognitive processes. We tested a group of current, ex, and nonkava users among an indigenous population in northern Australia, using saccade and cognitive tests that have proven cross-cultural validity and are sensitive to subtle disruptions of the brain arising from substance abuse or neuropsychiatric illness. Despite collecting data from among the heaviest reported kava drinkers in the world, we found no impairment in cognitive or saccade function in individuals who were currently heavy kava users (and had been for up to 18 years), nor was there any impairment in individuals who had been heavy kava users in the past but had abstained for longer than 6 months. Current and ex-kava users showed a higher rate of kava dermopathy, lower body mass index, lowered blood lymphocytes and, in addition, current kava users showed elevated liver enzymes. While there has recently been increasing concern about potentially fatal liver damage attributed to kava use, we have found no evidence of brain dysfunction in heavy and long-term kava users.
Adolescent↗
Use of terbinafine for tinea in Australian Aboriginal communities in the Top End.
Tinea of the skin and nails is a common problem in remote Aboriginal communities of the Top End of Australia. A retrospective study was performed on data collected from 104 patients from several indigenous communities. Worksheets were filled in by district medical officers and rural general practitioners, detailing the extent of the tinea. Patients were prescribed between 4 and 12 weeks of 250 mg daily oral terbinafine. Fifty-two patients were followed up, with 45 having a good response to treatment (87%) and with 22 of these patients having full clearance of tinea (42%). A prospective study with 44 subjects was performed. The extent of the tinea was documented and fungal scrapings/clippings were taken. Forty subjects were recruited and given oral terbinafine (2-12 weeks depending on skin/nail involvement) or topical terbinafine if oral treatment was contraindicated. Twenty-five of the 40 (63%) subjects were reviewed. Twenty-three (92%) subjects that were followed up improved clinically, with 8/25 (32%) clearing completely. Twenty (80%) of followed-up patients complied fully with treatment. Terbinafine was found to be a well-tolerated and effective treatment of tinea of the skin and nails.
Administration, Oral↗
Suspected snakebite: one year prospective study of emergency department presentations.
AIM: Snakebite is an uncommon, but potentially life-threatening condition. The more common clinical scenario is suspected snake-bite. Our aim was to characterise the epidemiology, diagnosis and management of patients with suspected snakebites. METHODS: Prospective cohort study of patients presenting with suspected snakebites to a tertiary referral hospital serving a large rural region in tropical northern Australia where a standard admission protocol for suspected snakebites is used. RESULTS: Of 70 suspected snakebite cases, there were 45 definite bites: three severe envenomings (two western brown snakes [Pseudonaja nuchalis] and one mulga snake [Pseudechis australis]); seven mild/moderate envenomings by other snakes, two non-envenomings by identified P. nuchalis, five bites by identified non-venomous snakes and 28 definite bites without envenoming. The remaining 25 cases were either suspected bites (8), unlikely bites (15) and two people hit by snakes. Definite snake-bites occurred throughout the year, peaking in May and December. There were three severe envenomings (mainly coagulopathy), requiring antivenom treatment, but no deaths or major complications. Most patients had appropriate investigations. Of 47 venom detection kit swabs collected, 34 were not tested, venom was not detected in nine and was positive in the three envenomings with one false-positive tiger snake. Whole blood clotting time was highly sensitive for procoagulant coagulopathy and envenoming in this study. Median length of time from the bite to discharge was 20 h (interquartile range: 12-27). CONCLUSIONS: The study shows that although suspected snakebite was common, severe envenoming occurred in less than 5% of cases. The study supports the proposition that a structured approach and admission policy of suspected snakebites leads to the appropriate management of severe envenoming, with no cases discharged early and no cases of non-envenoming treated with antivenom.
Adolescent↗
Mechanisms for a novel immune evasion strategy in the scabies mite sarcoptes scabiei: a multigene family of inactivated serine proteases.
Parasitic infestation of the skin by the mite Sarcoptes scabiei is a significant problem worldwide, particularly in socially disadvantaged communities. A multigene family of at least 24 homologs of a serine protease allergen have been identified in S. scabiei. Surprisingly, the products of all but one of these genes are predicted to be catalytically inactive, due to mutations at a critical triad of amino acids at the active site. We discuss the possibility that these genes for inactivated proteases have been conserved because they mediate a novel host defense evasion strategy that the mite has evolved as an adaptation to parasitism of the epidermis. The identification of this family, and elucidation of its value to the parasite, may present an unanticipated approach to protective vaccination.
Allergens↗
Clinical toxinology--where are we now?
Clinical toxinology encompasses a broad range of medical conditions resulting from envenomation by venomous terrestrial and marine organisms, and also poisoning from ingestion of animal and plant toxins. Toxin-related disease is an important cause of morbidity and mortality worldwide, particularly in the tropical and subtropical continents. Snake bite is the single most important toxin-related disease, causing substantial mortality in many parts of Africa, Asia, and the Americas. The most important snake families are Viperidae and Elapidae, causing a range of clinical effects including local necrosis, neurotoxicity, coagulopathy and hemorrhage, myotoxicity and renal toxicity. These effects vary according to geography and group of snake. Arachnid envenomation results mainly in morbidity, particularly scorpion stings which can cause severe systemic envenomation. Spider bite is far less of a problem, and the majority of medically important cases can be attributed to widow spiders (Latrodectus spp.) and recluse spiders (Loxosceles spp.). Marine-related envenomations are common, but severe effects are less so. Plant and mushroom poisoning occur in most parts of the world, but the types and methods of poisoning vary considerably between continents. Management of toxin-related disease is often difficult, and in many cases meticulous supportive care is all that is available. The mainstay of treatment is the use of antivenoms for many envenomations and poisoning, although these do not exist for all dangerous organisms. Unfortunately antivenoms are not an economically viable product, so development and manufacture of these agents have been limited. This is now further worsened by a current shortage of antivenom. There is a need for improvement in the preventionand management of toxin-related disease. This will require well-designed studies to define the extent of the problem, initiatives to improve the prevention and management of these conditions, and development of new, and continuation of current, antivenom supplies.
Animals↗
Marine antivenoms.
There is an enormous diversity and complexity of venoms and poisons in marine animals. Fatalities have occurred from envenoming by sea snakes, jellyfish, venomous fish such as stonefish, cone snails, and blue-ringed octopus. Deaths have also followed ingestion of toxins in shellfish, puffer fish (Fugu), and ciguatoxin-containing fish. However antivenoms are generally only available for envenoming by certain sea snakes, the major Australian box jellyfish (Chironex fleckeri) and stonefish. There have been difficulties in characterizing the toxins of C. fleckeri venom, and there are conflicting animals studies on the efficacy of C. fleckeri antivenom. The vast majority of C. fleckeri stings are not life-threatening, with painful skin welts the major finding. However fatalities that do occur usually do so within 5 to 20 minutes of the sting. This unprecedented rapid onset of cardiotoxicity in clinical envenoming suggests that antivenom may need to be given very early (within minutes) and possibly in large doses if a life is to be saved. Forty years of anecdotal experience supports the beneficial effect of stonefish antivenom in relieving the excruciating pain after stonefish spine penetration. It remains uncertain whether stonefish antivenom is efficacious in stings from spines of other venomous fish, and the recommendation of giving the antivenom intramuscularly needs reassessment.
Animals↗
Evolution of sfbI encoding streptococcal fibronectin-binding protein I: horizontal genetic transfer and gene mosaic structure.
Streptococcal fibronectin-binding protein is an important virulence factor involved in colonization and invasion of epithelial cells and tissues by Streptococcus pyogenes. In order to investigate the mechanisms involved in the evolution of sfbI, the sfbI genes from 54 strains were sequenced. Thirty-four distinct alleles were identified. Three principal mechanisms appear to have been involved in the evolution of sfbI. The amino-terminal aromatic amino acid-rich domain is the most variable region and is apparently generated by intergenic recombination of horizontally acquired DNA cassettes, resulting in a genetic mosaic in this region. Two distinct and divergent sequence types that shared only 61 to 70% identity were identified in the central proline-rich region, while variation at the 3' end of the gene is due to deletion or duplication of defined repeat units. Potential antigenic and functional variabilities in SfbI imply significant selective pressure in vivo with direct implications for the microbial pathogenesis of S. pyogenes.
Adhesins, Bacterial↗
Strains of Streptococcus pyogenes from severe invasive infections bind HEp2 and HaCaT cells more avidly than strains from uncomplicated infections.
Epidemiologically unrelated Streptococcus pyogenes strains isolated from blood, throat, and skin were assayed for adherence to HEp2 and HaCaT cells. Invasive isolates showed significantly higher avidity for these cell lines than isolates from skin and throat. In general, S. pyogenes showed greater binding to HaCaT cells than to HEp2 cells.
Bacterial Adhesion↗
Intensity of rainfall and severity of melioidosis, Australia.
In a 12-year prospective study of 318 culture-confirmed cases of melioidosis from the Top End of the Northern Territory of Australia, rainfall data for individual patient locations were correlated with patient risk factors, clinical parameters, and outcomes. Median rainfall in the 14 days before admission was highest (211 mm) for those dying with melioidosis, in comparison to 110 mm for those surviving (p=0.0002). Median 14-day rainfall was also significantly higher for those with pneumonia. On univariate analysis, a prior 14-day rainfall of 125 mm was significantly correlated with pneumonia (odds ratio [OR] 1.70 [confidence interval [CI] 1.09 to 2.65]), bacteremia (OR 1.93 [CI 1.24 to 3.02]), septic shock (OR 1.94 [CI 1.14 to 3.29]), and death (OR 2.50 [CI 1.36 to 4.57]). On multivariate analysis, rainfall in the 14 days before admission was an independent risk factor for pneumonia (p=0.023), bacteremic pneumonia (p=0.001), septic shock (p=0.005), and death (p<0.0001). Heavy monsoonal rains and winds may cause a shift towards inhalation of Burkholderia pseudomallei.
Adult↗
Melioidosis in northern Australia, 2001-02.
Melioidosis, caused by the gram negative bacterium Burkholderia pseudomallei, is endemic in northern Australia. Using data collated from centres in Western Australia, the Northern Territory and Queensland, this report describes the epidemiology of this disease between 1 November, 2001 and 31 October, 2002. There were 47 cases seen during this period with an average annual incidence of 5.8 cases per 100,000 population. In Indigenous Australians, an incidence of 25.5 cases per 100,000 population was seen. The timing and location of cases was generally correlated with rainfall across northern Australia. A case-cluster in a Queensland community was associated with post-cyclonic flooding. Risk factors included diabetes, alcohol-related problems and renal disease. Pneumonia (51%) was the most common clinical diagnosis. The mortality rate attributable to melioidosis was 21 per cent, although a number of other patients died of underlying disease. Despite improvements in recognition and treatment, melioidosis is still associated with a high morbidity and mortality, particularly in Indigenous Australians.
Adolescent↗
Rainfall and vector mosquito numbers as risk indicators for mosquito-borne disease in central Australia.
There have been 5 confirmed cases of Murray Valley encephalitis virus (MVE) infection in the Alice Springs region during the high rainfall years of 1999/00 and 2000/01, compared with one case in the preceding 9 years. There also appeared to be an increased prevalence of Ross River virus (RR) infection in the Alice Springs and Tennant Creek regions associated with high rainfall. This paper presents an analysis of summer rainfall from 1990/91 to 2000/01, numbers of seroconversion of sentinel chickens to MVE, and RR cases in both regions. In Alice Springs where summer rainfall (December to February) and average vector numbers in the December to March period are closely correlated, the analysis also included mosquito vector numbers and MVE cases. Summer rainfall over 100 mm was significantly associated with sentinel chicken seroconversions to MVE. From December to March there was also a significant association of average vector numbers (> or = 300) with seroconversions in sentinel chickens following high summer rainfall. MVE appears enzootic in the Tennant Creek region and epizootic in the Alice Springs region. In Alice Springs during December to March, there was a significant association of RR cases with rainfall over 100 mm and with average vector numbers over 300. There was also a significant correlation of summer rainfall with RR cases in Tennant Creek. Summer rainfall is a new and good early indicator of high risk for both MVE and RR disease in the Alice Springs locality and RR in the Tennant Creek locality. Although similar relationships between rainfall and vector abundance, and disease incidence probably exist in other areas of central Australia, rainfall and vector abundance thresholds will probably vary according to local climatic and environmental conditions.
Alphavirus Infections↗
Prevention of opportunistic infections in immunosuppressed patients in the tropical top end of the Northern Territory.
The population of the Top End of the Northern Territory has a high incidence of several infections of particular significance in the immunosuppressed. The following protocol for evaluation and treatment of patients prior to immunosuppression was developed in order to reduce the incidence of serious opportunistic infections. The infections discussed are Strongyloides stercoralis, tuberculosis, scabies, chronic hepatitis B, melioidosis and other bacterial infections. We recommend that all patients planned to receive more than 0.5 mg/kg/day of prednisolone for >14 days, or any more potent immunosuppressive drug, be evaluated and treated according to this protocol. Details of the rationale, evidence base, and proposed investigations and therapy for such patients are discussed.
AIDS-Related Opportunistic Infections↗
Identification of a homologue of a house dust mite allergen in a cDNA library from Sarcoptes scabiei var hominis and evaluation of its vaccine potential in a rabbit/S. scabiei var. canis model.
Sarcoptes scabiei ("itch mite") causes scabies, a disease of considerable human and veterinary significance. Little work has been done at the molecular level because of the difficulty of obtaining mites. We have used mites in skin from the bedding of crusted scabies patients for the construction of a library of 10(5) cDNAs from S. scabiei var. hominis cloned in the vector pGEX4T-2. We describe the isolation by immunoscreening of 2 clones, one of which (Ssagl) is homologous to and cross-reactive with the house dust mite Euroglyphus maynei allergen M-177, an apolipoprotein from hemolymph. Immunohistochemistry revealed that it is located around the internal organs and cuticle of the mite and in eggs. Although it was not found to be protective in a challenge trial, the rabbits did not exhibit typical crust characteristics. This work shows that it is now possible to conduct such challenge trials with cloned scabies antigens.
Allergens↗
Generation and characterization of cDNA clones from Sarcoptes scabiei var. hominis for an expressed sequence tag library: identification of homologues of house dust mite allergens.
Molecular studies on scabies, a disease of considerable human and veterinary significance, have been limited because of the difficulty of obtaining the causative organism Sarcoptes scabiei, the "itch mite." We have used skin from the bedding of crusted scabies patients as a source of mites for the construction of libraries of cDNAs from S. scabiei var. hominis in the bacteriophage lambda vector lambdaZAP express. Sequences of 145 clones established that the libraries predominantly contain sequences from S. scabiei, enabling a major sequencing program to begin. Among those sequenced to date, cDNAs encoding S. scabiei homologues of 3 house dust mite allergens-the M-177 apolipoprotein, glutathione S-transferase, and paramyosin--were identified. The availability of cDNA libraries from S. scabiei var. hominis and S. scabiei var. vulpes and the emerging public sequence databases from both opens up new possibilities in scabies research.
Allergens↗
Cystic Fibrosis and Burkholderia pseudomallei Infection: An Emerging Problem?
We recently managed 4 patients with cystic fibrosis who had acquired Burkholderia pseudomallei infection after exposure in a region of endemicity. Person-to-person transmission between 2 siblings may have occurred; otherwise, the evidence suggests that cystic fibrosis may increase the likelihood of infection with this organism, and patients should be warned of this possibility and cautioned to avoid high-risk activities.
Adult↗