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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

A DNA fingerprinting system for the ectoparasite Sarcoptes scabiei.

We describe multiple hypervariable microsatellites that will provide a highly informative genetic marker system for the sarcoptid mite Sarcoptes scabiei. Eighteen positive clones containing the highly repetitive sequence (GA)n were isolated from a partial genomic library of S. scabiei. Ten of these clones were characterised by sequencing and primers were designed from the unique sequences flanking eight microsatellite loci. Genomic DNA was subsequently extracted from individual mites and the repeat blocks were amplified by way of [gamma 33P] ATP end-labelled polymerase chain reaction. Fragment length polymorphisms were revealed in three of the loci when resolved on polyacrylamide sequencing gels. The high levels of allelic variability demonstrated between individual mites enable these three loci to form a DNA fingerprinting system that will be suitable for epidemiological and taxonomic studies both within and between host species.

Alleles

A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae.

In February 1995, single-dose azithromycin was given to children with trachoma and their household contacts who were children. For children with trachoma, rates of carriage of pneumococci immediately before treatment with azithromycin and 2-3 weeks, 2 months, and 6 months after treatment were 68% (54 of 79), 29% (11 of 38), 78% (29 of 37), and 87% (34 of 39), respectively. The proportion of carriage-positive children with azithromycin-resistant Streptococcus pneumoniae strains was 1 of 54 (1.9%) before treatment and then 6 of 11 (54.5%), 10 of 29 (34.5%), and 2 of 34 (5.9%) at follow-up visits. The profile of pneumococcal serotypes changed after azithromycin treatment. Azithromycin-resistant strains (serotypes 10F, 23A, and 45) were isolated from 1 (1.3%) of 79 pretreatment swab specimens, from 16 (21.3%) of 75 swab specimens collected up to 2 months after treatment, and from 2 (6%) of 32 obtained 6 months after treatment. Mathematical modeling showed a more rapid appearance of azithromycin-resistant pneumococcal strains in previously colonized children than in previously noncolonized children. Thus, it appears that the selective effect of azithromycin allowed the growth and transmission of preexisting azithromycin-resistant strains. More research is needed to clarify the clinical relevance and implications of azithromycin use.

Adolescent

Emerging epidemic of community-acquired methicillin-resistant Staphylococcus aureus infection in the Northern Territory.

OBJECTIVE: To investigate the epidemiology of WA MRSA (the recently recognised Western Australian strains of methicillin-resistant Staphylococcus aureus) in the north of the Northern Territory (NT). DESIGN: Retrospective survey of data from hospital records. SETTING: Royal Darwin Hospital (a tertiary referral hospital that serves the north of the NT) between January 1991 and July 1995. SUBJECTS: All inpatients with clinical MRSA infection. OUTCOME MEASURES: Incidence of MRSA infection, classification of MRSA as WA or EA (Eastern Australian) based on antibiotic susceptibility, patient demographic details (age, sex, ethnicity, region of residence), source of infection (nosocomial or community-acquired). RESULTS: There were 125 WA MRSA and 93 EA MRSA infections, comprising 7% of all S. aureus infections. The incidence of WA MRSA infections consistently increased, while that of EA MRSA initially fell and then increased. All EA MRSA infections were nosocomial, while 50% of WA MRSA infections were community-acquired. Rates of WA MRSA infections were highest in patients from the west region of the NT, adjacent to the Kimberley region of Western Australia (WA). Community-acquired WA MRSA infections were more likely to affect Aboriginals than non-Aboriginals (relative risk [RR], 25.86; 95% confidence interval [CI], 12.51-53.47, based on population data; RR, 15.43; 95% CI, 7.85-30.32, based on admission data), as were nosocomial EA MRSA infections (RR, 2.54; 95% CI, 1.44-4.47, based on population data; RR, 2.30; 95% CI, 1.52-3.46, based on admission data). CONCLUSIONS: Changes in the epidemiology of MRSA infection in the north of the NT are consistent with the hypothesis that community-acquired WA MRSA spread into and across the NT from the Kimberley region of WA. Alternatively, crowded living conditions, hygiene difficulties and increasing use of broad spectrum antibiotics may have led to independent emergence of WA MRSA in both regions. Current infection control policies and their use in rural Aboriginal communities must be reassessed.

Adolescent

Acute rheumatic fever and rheumatic heart disease in the top end of Australia's Northern Territory.

OBJECTIVE: To describe the epidemiological and clinical features of acute rheumatic fever and rheumatic heart disease in the Top End of the Northern Territory. METHODS: A retrospective review (in some instances as far back as the 1960s) of all cases of known or suspected acute rheumatic fever or rheumatic heart diseases, with prospective validation of clinical status where necessary. Cases were ascertained from hospital and community medical clinic records and medical staff; and from records and health staff of 10 rural communities. RESULTS: Three hundred and eighty-six revised Jones criteria-confirmed episodes of acute rheumatic fever were documented in 249 individuals (99% Aboriginal). The annual incidence of confirmed acute rheumatic fever between 1989 and 1993 was 254 per 100,000 Aboriginal people aged 5 to 14 years. A more accurate estimate of 651 per 100,000 came from 10 rural communities with more complete information. As of 1995, there were 286 people living with established rheumatic heart disease (95% Aboriginal). The point prevalence of rheumatic heart disease among Aboriginal people was 9.6 per 1000, with a rate of 24 per 1000 in one large rural community. Sydenham's chorea was common, and associated with later rheumatic heart disease in 49% of cases. There was a preponderance of females with acute rheumatic fever, rheumatic heart disease and chorea. CONCLUSIONS: In Aboriginal people in rural northern Australia the incidence of acute rheumatic fever is higher than that reported anywhere in the world, and the prevalence of rheumatic heart disease is among the highest in the world. While continuing attention must be paid to alleviating the causes of these diseases of poverty, immediate action is needed to improve diagnosis of acute rheumatic fever, adherence to secondary benzathine penicillin prophylaxis regimens, and follow-up of rheumatic heart disease cases.

Chorea

An 18 year clinical review of septic arthritis from tropical Australia.

A retrospective study of 191 cases of septic arthritis was undertaken at Royal Darwin Hospital in the tropical north of Australia. Incidence was 9.2 per 100,000 overall and 29.1 per 100,000 in Aboriginal Australians (RR 6.6; 95% CI 5.0-8.9). Males were affected more than females (RR 1.6; 95% CI 1.2-2.1). There was no previous joint disease or medical illness in 54%. The commonest joints involved were the knee (54%) and hip (13%). Significant age associations were infected hips in those under 15 years and infected knees in those over 45 years. Seventy two percent of infections were haematogenous. Causative organisms included Staphylococcus aureus (37%), Streptococcus pyogenes (16%) and Neisseria gonorrhoeae (12%). Unusual infections included three melioidosis cases. Polyarthritis occurred in 17%, with N. gonorrhoeae (11/23) more likely to present as polyarthritis than other organisms (22/168) (OR 6.0; 95% CI 2.1-16.7). Univariate and multivariate analysis showed the hip to be at greater risk for S. aureus than other joints. Open arthrotomy was a more successful treatment procedure than arthroscopic washout or needle aspiration.

Adolescent

Streptococcus pneumoniae carriage and penicillin/ceftriaxone resistance in hospitalised children in Darwin.

BACKGROUND: The prevalence of resistant Streptococcus pneumoniae (SP) is increasing world-wide. Pneumococcal prevalence and susceptibility patterns are not known for children in the Top End of the Northern Territory. AIMS: To determine the prevalence of nasopharyngeal carriage of pneumococci in children hospitalised in Darwin, and the extent of penicillin and ceftriaxone resistance in these isolates. METHODS: Nasopharyngeal swabs were collected on admission from 85 children who had not received antimicrobials for their admission illness. Antimicrobial resistance was determined following selective culture for SP isolates. Minimal inhibitory concentrations (MICs) for penicillin and ceftriaxone were determined using the E-test method. RESULTS: The overall prevalence of nasopharyngeal SP carriage was 44%. Carriage occurred more often in Aboriginal children from rural areas (56%) than in urban children (24%) (OR 3.94, 95% CI 1.35-11.78, p < 0.01). Thirty per cent of isolates were penicillin resistant, 35% were ceftriaxone resistant, and 49% were resistant to at least one of these. One isolate showed high-level resistance to both antimicrobials; all other resistant isolates were of intermediate-level resistance. For the same isolate, MICs for ceftriaxone were more often higher than those for penicillin. Five isolates had intermediate resistance to ceftriaxone whilst remaining sensitive to penicillin. CONCLUSIONS: The prevalence of pneumococcal resistance to penicillin and ceftriaxone in hospitalised children in Darwin is much higher than previously reported in Australia. This has implications for future antimicrobial management and highlights the need for regular regional surveillance of SP resistance. The development of conjugate pneumococcal vaccines for children under two years is a priority.

Ceftriaxone

Towards understanding the pathogenesis of rheumatic fever.

Acute rheumatic fever results from an immunological response to group A streptococcal infection, but the exact nature of this response, and of the underlying host and organism characteristics, continues to evade researchers. Earlier models of rheumatic fever pathogenesis emphasised the importance of humoral immunity, but more recent work suggests that cellular immunity may play a primary role. Greater understanding of these disease mechanisms is allowing researchers to move towards the development of a vaccine for rheumatic fever.

Humans

An evaluation of unleaded petrol as a harm reduction strategy for petrol sniffers in an aboriginal community.

OBJECTIVE: In mid 1989, leaded petrol was replaced by unleaded petrol to reduce lead toxicity in petrol sniffers in Maningrida, a remote Aboriginal community in Northern Australia. RETROSPECTIVE REVIEWS: Hospital admissions between 1987 and 1992 due to petrol sniffing were compared for Maningrida and a community using only leaded petrol. RESULTS: Admissions from Maningrida decreased significantly following introduction of unleaded petrol (chi 2 on 2df = 22.25, p < 0.001). Lead and hydrocarbon exposures were also compared for three groups from Maningrida (27 sniffers using only unleaded petrol; 15 exsniffers and 13 nonsniffers) and 24 individuals admitted to hospital for petrol sniffing related illness from other communities using only leaded petrol. Median blood lead levels for hospitalized sniffers (using only leaded petrol). Maningrida sniffers (using only unleaded petrol), exsniffers and nonsniffers were 5.06, 1.87, 1.24 and 0.17 microM/L respectively. There were significant differences between blood lead level, delta-aminolevulinic acid dehydratase activity, and free erythrocyte protoporphyrin for sniffers of leaded and unleaded petrol, whereas these indices were not significantly different for current sniffers and exsniffers in Maningrida. Hydrocarbons were only detectable in the blood of active sniffers (toluene < or = 0.5 micrograms/mL; benzene < or = 0.17 micrograms/mL blood; n-hexane not detected). CONCLUSIONS: The elimination of tetraethyl lead from petrol resulted in a significant decrease in hospitalization of petrol sniffers.

Adolescent

Are the currently recommended doses of benzathine penicillin G adequate for secondary prophylaxis of rheumatic fever?

OBJECTIVE: To review the literature on dose and regimens of intramuscular benzathine penicillin G (BPG) for secondary prophylaxis of recurrent rheumatic fever. SETTING: For over 40 years BPG has been the gold standard for secondary prophylaxis, usually as a dose of 1,200,000 U (900 mg). Although studies have suggested that BPG injections every 3 weeks are superior to injections every 4 weeks, implementation of an every 3 weeks regimen can be problematic with regards to both patient compliance (adherence) and an increased burden on health resources. FINDINGS: Some of the earliest studies of BPG suggested that larger doses resulted in prolongation of detectable penicillin levels. A recent study assessing plasma penicillin levels after BPG doses of 1,200,000 U, 1,800,000 U, and 2,400,000 U suggested there may be benefits in a BPG regimen every 4 weeks with doses higher than the standard 1,200,000 U. CONCLUSIONS: Further studies of higher dose BPG regimens seem justified. In addition, further work is needed on quality and storage options for different BPG preparations; location and method of BPG injections; the importance of weight differences between individuals; and ways of improving access to and compliance with BPG regimens.

Anti-Bacterial Agents

Evaluation of strategies used by a remote aboriginal community to eliminate petrol sniffing.

OBJECTIVE: To evaluate the success of strategies--including replacing petrol with aviation gasoline (avgas) in the fuel supply, and employment and skills-training programs targeting young people--in reducing petrol sniffing at Maningrida, an isolated Aboriginal community in northern Australia. METHODS: A follow-up study of 13 Aboriginals who were non-sniffers, 15 who were ex-sniffers and 27 who were petrol sniffers in 1992 was conducted by questionnaire in 1994, 20 months after intervention strategies were commenced; 11 non-sniffers, 11 ex-sniffers and 18 petrol sniffers, respectively, participated. MAIN OUTCOME MEASURES: Petrol-sniffing status, changes in employment status, blood lead levels of the participants, and community crime statistics. RESULTS: After intervention strategies in Maningrida, petrol sniffing ceased, with related crime falling markedly. Employment increased significantly among petrol sniffers, from 7% to 63% (chi 2 = 11.53; df = 1; P < 0.001). Only two petrol sniffers were reported to have continued petrol sniffing elsewhere. Apart from one of these individuals, who had recently returned to Maningrida, blood lead levels fell significantly in those with a history of petrol sniffing, indicating they had not continued to sniff avgas, which contains lead additives (0.8 g/L). CONCLUSIONS: While avgas introduction was a key element in eliminating petrol sniffing, its apparent lack of success as a single intervention elsewhere indicates the importance of widespread community resolve against petrol sniffing and the development of coordinated employment strategies in successfully eliminating the practice and reducing associated social disruption.

Adolescent

Identification of Chironex fleckeri envenomation by nematocyst recovery from skin.

OBJECTIVE: To prospectively compare two methods of nematocyst retrieval from skin for confirmation of Chironex fleckeri jellyfish envenomation. PARTICIPANTS AND METHODS: Twenty patients presenting to Royal Darwin Hospital with jellyfish stings. In each, two methods of retrieval of nematocysts from the sting site were tested: scraping the skin with a scalpel blade; and application of transparent sticky tape. RESULTS: Chironex fleckeri nematocysts were identified in 14/20 patients by scalpel blade scraping and in 17/20 by the sticky tape method. In all patients with scalpel blade scrapings positive for nematocysts, nematocysts were also retrieved by the sticky tape method. Only four patients required narcotic analgesia and none required C. fleckeri antivenom. CONCLUSIONS: Nematocyst retrieval from skin by a simple sticky tape method is at least as good as scraping with a scalpel blade. Chironex fleckeri causes the majority of jellyfish envenomations presenting to Royal Darwin Hospital.

Adolescent

Characterisation of group A streptococcal isolates from tropical Australia with high prevalence of rheumatic fever: probing for signature sequences to identify members of the family of serotype 5.

The prevalence of rheumatic heart disease (RHD) in Northern Territory Aboriginal communities is high, but there is a low isolation rate of historically rheumatic fever associated M types (such as M5) of group A streptococci (GAS). Many isolates are M non-typable (MNT). Serology suggests that the population is exposed to M5-like isolates; some RHD patients having high IgM or IgG titres to two M5 B-repeat region peptide epitopes, B1 (KQQESK) and B4 (EQKSKQ). To identify relatives of M5 in our collection of GAS, oligonucleotide probes to the B1 and B4-repeat regions shared by M5 and a local M5-like isolate, were used to screen 101 isolates for the presence of signature sequences. In all, 28% of the tropical Australian isolates contained the signature sequences, identifying members of the M5 family. The 5' region of the genes for M proteins from three members of the M5 family fell into two sequence types. Hybridisation to probes based on these sequences suggested that among tropical Australian isolates there are at least three distinct sequence types that contained the M5 signature sequences. These results suggest that a considerable number of M5 family GAS are circulating in tropical Australia.

Amino Acid Sequence