Biomedical subjects

B J Currie

Publications and source records attributed to B J Currie.

At least 55 records · Page 3Linked to original sources

PubMed2001

A cluster of melioidosis cases from an endemic region is clonal and is linked to the water supply using molecular typing of Burkholderia pseudomallei isolates.

Nine cases of melioidosis with four deaths occurred over a 28-month period in members of a small remote Aboriginal community in the top end of the Northern Territory of Australia. Typing by pulsed-field gel electrophoresis showed isolates of Burkholderia pseudomallei from six of the cases to be clonal and also identical to an isolate from the community water supply, but not to soil isolates. The clonality of the isolates found in this cluster contrasts with the marked genetic diversity of human and environmental isolates found in this region which is hyperendemic for B. pseudomallei. It is possible that the clonal bacteria persisted and were propagated in biofilm in the water supply system. While the exact mode of transmission to humans and the reasons for cessation of the outbreak remain uncertain, contamination of the unchlorinated community water supply is a likely explanation.

Burkholderia pseudomallei↗

PubMed2001

Therapy of uncomplicated falciparum malaria: a randomized trial comparing artesunate plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone in Irian Jaya, Indonesia.

Combining artesunate with existing antimalarial drugs may improve cure rates, delay emergence of resistance, and reduce transmission. We performed a randomized comparative trial to quantify the effect of adding artesunate to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in Indonesia. Using a modified 1997 World Health Organization protocol for assessment of therapeutic efficacy of antimalarial drugs, 105 patients (stratified by age/ethnic group) were randomized: 53 received artesunate orally, 4 mg/kg of body weight, a single daily dose for three days, plus sulfadoxine-pyrimethamine orally (1.25 mg of pyrimethamine/kg of body weight), a single dose on day 0, and 52 patients received sulfadoxine-pyrimethamine alone. Six from the combination group were withdrawn from analysis, as were six of the sulfadoxine-pyrimethamine group. Treatment failure rates on day 14 were 0% in the artesunate plus sulfadoxine-pyrimethamine group and 8.7% in the sulfadoxine-pyrimethamine group (P = 0.12). Treatment failure rates on day 28 were 4.4% and 15.2%, respectively (P = 0.16). Relative risk of treatment failure at 28 days was 0.3 (95% confidence interval [CI] = 0.1-1.3). Mean fever clearance time (1.3 versus 1.7 days) and mean parasite clearance time (1.4 versus 2.0 days) were both faster in the artesunate plus sulfadoxine-pyrimethamine group than in the sulfadoxine-pyrimethamine group (P = 0.08 and P < 0.0001, respectively). Only 20 (39.2%) of 51 patients treated with artesunate plus sulfadoxine-pyrimethamine were still parasitemic on day 1 compared with 45 (86.5%) of 52 patients treated with sulfadoxine-pyrimethamine alone (P = 0.000001, relative risk [RR] = 0.4, 95% CI = 0.3-0.6). Gametocyte carriage was lower following artesunate plus sulfadoxine-pyrimethamine than following sulfadoxine-pyrimethamine (RR = 0.5, 95% CI = 0.2-1.0 on day 7 and RR = 0.5, 95% CI = 0.2-1.1 on day 14). Mild diarrhea, rash, and itching resolved without treatment. Combined artesunate plus sulfadoxine-pyrimethamine resulted in more rapid fever and parasiteclearance, was well tolerated, reduced risk of treatment failure, and lowered gametocyte carriage.

Administration, Oral↗

PubMed2001

Fatal human melioidosis acquired in a subtropical Australian city.

We describe an acute fatal human case of melioidosis acquired in Ipswich, a city at 27.5 degrees S in southern Queensland, south of the area traditionally considered endemic for melioidosis in Australia. Molecular typing revealed that this patient isolate was genetically distinct from 2 other human and 1 bovine isolates of Burkholderia pseudomallei from the same region and from 4 tropical northern Australian strains. This finding suggests that if B. pseudomallei has been introduced to the region from northern Australia, it was not in recent times, and there has not been a point source of infection. Burkholderia pseudomallei is present in temperate southern Queensland, which hitherto has not been well appreciated. Clinicians should consider the diagnosis of acute melioidosis in patients with severe pneumonia or septicemia acquired in subtropical areas such as southern Queensland, particularly after heavy summer rains with flooding.

Animals↗

PubMed2001

Detection of histidine rich protein 2 and panmalarial ICT Malaria Pf/Pv test antigens after chloroquine treatment of uncomplicated falciparum malaria does not reliably predict treatment outcome in eastern Indonesia.

In regions with drug-resistant malaria, the ability to rapidly detect or predict treatment failure (TF) soon after a course of standard therapy for Plasmodium falciparum malaria would facilitate the prompt institution of second-line therapy. We thus evaluated longitudinally the ability of the ICT Malaria Pf/Pv immunochromatographic test to predict treatment outcome. Sixty-six Sumbanese Indonesians with uncomplicated falciparum malaria were treated with chloroquine and followed for 28 days by use of 1997 World Health Organization criteria for assessment of therapeutic efficacy of antimalarial drugs. The ICT Pf/Pv testing could be compared with microscopy in approximately half of the patients on each day of follow-up. Although strongly positive histidine rich protein 2 (HRP2) line intensities (equal to or greater than the control band) in convalescence were highly predictive of TF, any degree of positivity for the HRP2 and panmalarial antigens in convalescence was only moderately predictive of TE Positive predictive values of the HRP2 and panmalarial antigens for TF were 76.9% and 87.0%, respectively, on Day 3, 82.4% and 87.5% on Day 7, and 78.9% and 78.9% on Day 14. Negative HRP2 and panmalarial antigen results in convalescence were even less predictive of an adequate clinical response, and false-negative HRP2 and panmalarial antigen test results were found in one-sixth (6 of 37) of recrudescent infections diagnosed by microscopy among patients with late treatment failure. To reliably predict treatment outcome with rapid antigen tests, further development appears necessary to improve sensitivity for viable asexual parasites while avoiding detection of both gametocytes and persistent antigen in convalescence.

Antigens, Protozoan↗

PubMed2000

Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature.

In a prospective study of melioidosis in northern Australia, 252 cases were found over 10 years. Of these, 46% were bacteremic, and 49 (19%) patients died. Despite administration of ceftazidime or carbapenems, mortality was 86% (43 of 50 patients) among those with septic shock. Pneumonia accounted for 127 presentations (50%) and genitourinary infections for 37 (15%), with 35 men (18%) having prostatic abscesses. Other presentations included skin abscesses (32 patients; 13%), osteomyelitis and/or septic arthritis (9; 4%), soft tissue abscesses (10; 4%), and encephalomyelitis (10; 4%). Risk factors included diabetes (37%), excessive alcohol intake (39%), chronic lung disease (27%), chronic renal disease (10%), and consumption of kava (8%). Only 1 death occurred among the 51 patients (20%) with no risk factors (relative risk, 0.08; 95% confidence interval, 0.01-0.58). Intensive therapy with ceftazidime or carbapenems, followed by at least 3 months of eradication therapy with trimethoprim-sulfamethoxazole, was associated with decreased mortality. Strategies are needed to decrease the high mortality with melioidosis septic shock. Preliminary data on granulocyte colony-stimulating factor therapy are very encouraging.

Adolescent↗

PubMed2000

Nontuberculous mycobacterial disease in northern Australia: a case series and review of the literature.

We performed a retrospective/prospective review of all cases of disease due to nontuberculous mycobacteria (NTM) reported in the Northern Territory, Australia, during the period 1989-1997. Fifty-eight cases were reported, with an average yearly incidence of 3.9 cases per 100,000 persons. The number increased significantly for the second half of the study period (39 vs. 19 cases; P<.02). The yearly incidence of pulmonary Mycobacterium avium/Mycobacterium intracellulare complex (MAC) disease not associated with human immunodeficiency virus (HIV) infection was 2.1 cases per 100,000 population. MAC was the most common isolate (78%) and pulmonary disease the most frequent clinical presentation (62%). Disease due to NTM or MAC was not found more commonly in rural areas. Significant risks for non-HIV-associated pulmonary MAC disease included male sex (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0-4.5) and age >50 years (OR, 26.5; 95% CI, 10.9-67.3), but aboriginal people appeared underrepresented (OR, 0.77; 95% CI, 0.30-1.87). Mycobacterium tuberculosis was almost 5 times more likely than NTM to be the cause of non-HIV-associated mycobacterial pulmonary disease (153 vs. 32 cases; OR, 4.79; 95% CI, 3.22-7.14). Mycobacterial lymphadenitis in aboriginal children was more likely to be tuberculous than nontuberculous (OR, 6.5; 95% CI, 1.4-41.7), but not in nonaboriginal children (OR, 1.0). With treatment, 66% of the cases of non-HIV-associated pulmonary MAC disease had favorable outcomes, and 7% of patients had progressive fatal disease. Outcomes of therapy for lymphadenitis and skin/soft-tissue disease were excellent, but those of HIV-associated disseminated MAC disease were poor.

AIDS-Related Opportunistic Infections↗

PubMed2000

Pharyngeal carriage of group C and group G streptococci and acute rheumatic fever in an Aboriginal population.

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) represent an autoimmune response to group A streptococcal pharyngitis. In the Aboriginal population of the Northern Territory of Australia, some of the highest rates of ARF in the world have been reported, although throat carriage rates of group A streptococcus in this population are extremely low and symptomatic group A streptococcal pharyngitis is uncommon; by contrast, carriage rates of group C and G streptococci are high. Therefore, we questioned the involvement of these groups in ARF and showed that they have the potential to elicit an autoimmune response that may trigger ARF.

Adult↗

PubMed2000

Contrasting molecular epidemiology of group A streptococci causing tropical and nontropical infections of the skin and throat.

Disease caused by group A streptococci (GAS) in tropical regions often takes the form of impetigo, whereas pharyngitis tends to predominate in temperate zones. GAS derived from asymptomatic throat infections and pyoderma lesions of rural Aboriginal Australians were evaluated for phylogenetic distant emm genes, which represent ecological markers for tissue site preference. On the basis of the percentage of total isolates from a given tissue, emm pattern A-C organisms exhibited a stronger predilection for the throat, whereas pattern D organisms preferred the skin. Only 16% of isolates collected by active surveillance displayed pattern A-C, which reflects the low incidence of oropharyngeal infection. Importantly, most (70%) pattern A-C organisms were isolated from skin sores, despite their innate tendency to infect the throat. Combined with findings from nontropical populations, analysis of the data supports the hypothesis that GAS tissue preferences are genetically predetermined and that host risk factors for infection strongly influence the differential reproduction of individual clones.

Adult↗

PubMed2000

A targeted, single-dose azithromycin strategy for trachoma.

OBJECTIVE: To evaluate the impact of treating children with acute trachoma and their contacts with oral azithromycin. DESIGN: Open, uncontrolled, prospective evaluation of a community-based treatment strategy. SETTING: Central Australian semi-desert Aboriginal community (1995-1996). PARTICIPANTS: 216 school- and pre-schoolchildren aged 6 months and up to 15 years. INTERVENTION: All children with acute trachoma and their contacts (co-resident siblings aged between 6 months and 15 years) received single-dose oral azithromycin suspension (20 mg/kg, to a maximum of 1000 mg). MAIN OUTCOME MEASURE: Prevalence of acute trachoma (World Health Organization trachoma diagnostic criteria). RESULTS: Trachoma prevalence at baseline was 42% (71/169) and 55% (18/33) for schoolchildren and pre-schoolchildren, respectively: 103 schoolchildren and 21 pre-schoolchildren, comprising 77 with follicular trachoma and their 47 contacts, were treated with azithromycin over an 8-week period. Acute trachoma prevalence in schoolchildren fell to 22% at 6-8 months (P < 0.0001) and was 31% at 12 months (P < 0.05 compared with baseline). Pre-schoolchildren were followed up for 6 months after treatment, and their trachoma prevalence fell from 55% to 25% (P < 0.05). Further treatment was given to children with trachoma at 12 months, and the point prevalence of trachoma for schoolchildren at 24 months was 34%. CONCLUSIONS: In contrast to mass-treatment strategies, significant reductions in trachoma prevalence at 6 months were achieved by screening 35% of community members (216) and treating 20% (124). The subsequent prevalence increases support the need for more comprehensive treatment programs, including health promotion and efforts to improve living conditions.

Acute Disease↗

PubMed2000

The epidemiology of melioidosis in Australia and Papua New Guinea.

Melioidosis was first described in Australia in an outbreak in sheep in 1949 in north Queensland (22 degrees S). Human melioidosis was first described from Townsville (19 degrees S) in 1950. Melioidosis is hyperendemic in the Top End of the Northern Territory (NT) and as in parts of northeastern Thailand it is the commonest cause of fatal community-acquired septicemic pneumonia. In the 9 years since 1989 the prospective NT melioidosis study at Royal Darwin Hospital (12 degrees S) has documented 206 culture confirmed cases of melioidosis, with an average annual incidence of 16.5/100,000. Melioidosis is also seen in the north of Western Australia and north Queensland, including the Torres Strait Islands, but is uncommon in adjacent Papua New Guinea. Serological studies suggest that infection is rare in the Port Moresby region, but there is emerging evidence of melioidosis from Western Province. The NT study has documented inoculating events in 52 (25%) of cases, with an incubation period of 1-21 days (mean 9 days); 84% of cases had acute disease from presumed recent acquisition and 13% had chronic disease (sick, > 2 months). In 4% there was evidence of possible reactivation from a latent focus; 28 of 153 (18%) males had prostatic abscesses. The overall mortality was 21% (43 cases), with a mortality rate in septicemic cases (95) of 39% and in non-septicemic cases (103) of 4%. Pneumonia was the commonest presentation in both groups and, in addition, eight patients (two deaths) presented with melioidosis encephalomyelitis. Melioidosis clusters in temperate Australia are attributed to animals imported from the north. Molecular typing of Burkholderia pseudomallei isolates from temperate southwest Western Australia showed clonality over 25 years. In this outbreak and in studies from the NT, some soil isolates are molecularly identical to epidemiologically related animal and human isolates. Molecular typing has implicated the water supply in two clonal outbreaks in remote aboriginal communities in northern Australia. Further prospective collaborative studies are required to evaluate whether there are truly regional differences in clinical features of melioidosis and to better understand how B. pseudomallei is acquired from the environment.

Animals↗

PubMed2000

Neurological melioidosis.

Neurological abnormalities have long been recognised in animals with melioidosis, including laboratory rodents and sheep in the first Australian outbreak in 1949. Autopsies in animals have shown microabscesses and lymphocytic infiltration to be present on occasion in the same animal, but Burkholderia pseudomallei is usually able to be grown from central nervous system (CNS) tissue. In humans CNS melioidosis is unusual, but both macroscopic brain abscesses and encephalitis occur. There has been a recently recognised syndrome of meningoencephalitis with varying involvement of brainstem, cerebellum and spinal cord. The prospective melioidosis study at Royal Darwin Hospital has documented 12 cases of CNS melioidosis over 9 years out of a total of 232 cases of melioidosis (5%). Prominent features on presentation were unilateral limb weakness (6), predominant cerebellar signs (2), mixed cerebellar and brainstem features with peripheral weakness (2) and flaccid paraparesis (2). Eight patients had unilateral VIIth nerve palsy and six bulbar palsy, with five requiring prolonged ventilation. Brain CT scans are usually normal initially, but MRI shows dramatic changes. Three patients died and only three made a full recovery. In two patients with predominant mononuclear CSF pleocytosis, B. pseudomallei was cultured from CSF and autopsy in one of these showed necrotising encephalitis with microabscesses. Although it has been postulated that a neurotropic exotoxin may account for melioidosis encephalomyelitis, the recent findings and comparison with the animal data suggest that direct organism spread within the CNS may be primarily responsible. Preliminary molecular typing of isolates shows no evidence of a specific strain of B. pseudomallei responsible for CNS melioidosis end further studies are required to determine if the apparent higher rate of CNS disease in Australia is due to true regional differences or is from increased ascertainment.

Adult↗

PubMed2000

Animal melioidosis in Australia.

Melioidosis was first diagnosed in Australia in sheep in 1949. While it has been considered endemic in tropical Australia, there have been animal outbreaks in southwest Western Australia and southern Queensland. Infection occurs in many species, with both latency and a wide range of clinical manifestations. Some species may develop melioidosis only if immunocompromised. Sheep and goats are particularly susceptible, resulting in the requirement for pasteurisation of tropical commercial goat's milk. Nine out of 43 (21%) goats had aortic lesions at autopsy and seven died from aortic aneurysm rupture. Transplacental transmission in goats has also been documented. Asymptomatic organ abscesses are common in pigs but bovine melioidosis is very rare. Camels moved north and an alpaca brought to Darwin have died from melioidosis. It also occurs in wildlife, including birds, crocodiles and kangaroos. Zoonotic transmission to humans is extremely unusual, but there are many similar epidemiological and clinical features of melioidosis in animals and humans. There have been three possible zoonotic cases in Australia. Molecular typing has found identical Burkholderia pseudomallei organisms from animals, humans and soil. The study of melioidosis in animals, especially the use of molecular genetic techniques for organism identification and typing, will continue to unravel aspects of the disease that remain unclear in humans.

Animals↗

PubMed2000

Cumulative incidence of rheumatic fever in an endemic region: a guide to the susceptibility of the population?

Aboriginal Australians in northern Australia are subject to endemic infection with group A streptococci, with correspondingly high rates of acute rheumatic fever and rheumatic heart disease. For 12 communities with good ascertainment, the estimated lifetime cumulative incidence of acute rheumatic fever was approximately 5.7%, whereas over the whole population, with less adequate ascertainment, the cumulative incidence was only 2.7%. The corresponding prevalences of established rheumatic heart disease were substantially less than the cumulative incidences of acute rheumatic fever, at least in part because of poor ascertainment. The cumulative incidence of acute rheumatic fever estimates the proportion of susceptible individuals in endemically exposed populations. Our figures of 2.7-5.7% susceptible are consistent with others in the literature. Such comparisons suggest that the major part of the variation in rheumatic fever incidence between populations is due to differences in streptococcal exposure and treatment, rather than to any difference in (genetic) susceptibility.

Acute Disease↗

PubMed2000

Skin infections and infestations in Aboriginal communities in northern Australia.

The most important skin infections in Aboriginal communities in central and northern Australia are scabies and streptococcal pyoderma. Scabies is endemic in many remote Aboriginal communities, with prevalences in children up to 50%. The cycles of scabies transmission underlie much of the pyoderma. Up to 70% of children have skin sores, with group A streptococcus (GAS) the major pathogen. Group A streptococcus is responsible for the continuing outbreaks of post-streptococcal glomerulonephritis and acute rheumatic fever (ARF). The cycles of scabies transmission in dogs and humans do not appear to significantly overlap. Guidelines have been developed for community control of scabies and skin sores and successful community initiated coordinated programmes have occurred. The anthropophilic dermatophyte Trichophyton rubrum is ubiquitous in many communities, again reflecting living conditions. Other skin infections related to the tropical environment include melioidosis, nocardiosis, Chromobacterium violaceum and chromoblastomycosis. Sustainable and long-term improvements in scabies, skin sores and GAS-related disease and tinea require fundamental changes that address social and economic inequities and, in particular, living conditions and overcrowding.

Adult↗

PubMed2000

Clinical toxicology: a tropical Australian perspective.

Tropical Australia has an amazing diversity of venomous fauna, from "the world's most venomous creature," the multi-tentacled (chirodropid) box jellyfish Chironex fleckeri, to aggressive spiders whose venom remains to be characterized. All genera of highly venomous Australasian elapid snakes are present, except for tiger snakes. Most notable is the taipan (Oxyuranus scutellatus), with the most efficient "snap-release" biting mechanism of any snake and venom components causing the full constellation of clinical envenoming features: coagulopathy from fibrinogen depletion (procoagulant), neurotoxicity (predominantly presynaptic neurotoxin) and rhabdomyolysis (myotoxin). Brown snakes (Pseudonaja textilis and P. nuchalis) now account for most snake bite fatalities in Australia, as a result of severe coagulopathy and a poorly defined early scenario of collapse, postulated to be caused by profound hypotension caused by transient myocardial dysfunction associated with prothrombin activation. Other venomous entities include paralyzing ticks, the blue-ringed octopus, stone fish and other marine animals with venomous spines, paralyzing cone shells, and a wide range of jellyfish including Carukia barnesi and possibly other four-tentacled (carybdeid) box jellyfish causing the Irukandji syndrome.

Animals↗

PubMed2000

Distribution and antigenicity of fibronectin binding proteins (SfbI and SfbII) of Streptococcus pyogenes clinical isolates from the northern territory, Australia.

Fibronectin binding proteins play an important role in the adherence and invasion of group A streptococci (GAS). Genotypically distinct GAS isolates were screened for the presence and expression of two streptococcal fibronectin binding protein genes, sfbI and sfbII. Of the tested strains, 64 and 36% were shown to harbor and express the sfbI and sfbII genes, respectively. All sfbII-positive strains tested were also positive for sfbI, but only 28% of the sfbII-negative strains were positive for sfbI. High levels of immunoglobulin G antibodies to both SfbI and SfbII were found in sera from 80 subjects with defined streptococcal infections.

Adhesins, Bacterial↗

PubMed1999

Clinical and epidemiological features of group A streptococcal bacteraemia in a region with hyperendemic superficial streptococcal infection.

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.

Adolescent↗

PubMed1999

Acute melioidosis outbreak in Western Australia.

A cluster of acute melioidosis cases occurred in a remote, coastal community in tropical Western Australia. Molecular typing of Burkholderia pseudomallei isolates from culture-confirmed cases and suspected environmental sources by pulsed-field gel electrophoresis (PFGE) of XbaI chromosomal DNA digests showed that a single PFGE type was responsible for five cases of acute infection in a community of around 300 during a 5 week period. This temporal and geographical clustering of acute melioidosis cases provided a unique opportunity to investigate the environmental factors contributing to this disease. B. pseudomallei isolated from a domestic tap at the home of an asymptomatic seroconverter was indistinguishable by PFGE. Possible contributing environmental factors included an unusually acid communal water supply, unrecordable chlorine levels during the probable exposure period, a nearby earth tremor, and gusting winds during the installation of new water and electricity supplies. The possible role of the potable water supply as a source of B. pseudomallei was investigated further.

Acute Disease↗