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Biomedical subjects

B J Currie

Publications and source records attributed to B J Currie.

At least 37 records · Page 2Linked to original sources

Melioidosis: an important cause of pneumonia in residents of and travellers returned from endemic regions.

Melioidosis is endemic in South East Asia, Asia and northern Australia. Infection usually follows percutaneous inoculation or inhalation of the causative bacterium, Burkholderia pseudomallei, which is present in soil and surface water in the endemic region. While 20-36% of melioidosis cases have no evident predisposing risk factor, the vast majority of fatal cases have an identified risk factor, the most important of which are diabetes, alcoholism and chronic renal disease. Half of all cases present with pneumonia, but there is great clinical diversity, from localised skin ulcers or abscesses without systemic illness to fulminant septic shock with multiple abscesses in the lungs, liver, spleen and kidneys. At least 10% of cases present with a chronic respiratory illness (sick > 2 months) mimicking tuberculosis and often with upper lobe infiltrates and/or cavities on chest radiography. As with tuberculosis, latency with reactivation decades after infection can also occur, although this is rare. Confirmation of diagnosis is by culture of B. pseudomallei from blood, sputum, throat swab or other samples. Microbiology laboratories need to be informed of the possibility of melioidosis, as those not familiar with it can misidentify the organism. Antibiotic therapy is initial intensive therapy with i.v. ceftazidime or meropenem or imipenem +/- cotrimoxazole for > or = 10 days, followed by eradication therapy with cotrimoxazole +/- doxycycline +/- chloramphenicol (first 4 weeks only) for > or = 3 months. Melioidosis has been increasingly recognised in returning travellers in Europe and recently melioidosis and colonisation with B. pseudomallei have been documented in cystic fibrosis patients visiting or resident in endemic areas.

Alcoholism↗

Streptococcus pyogenes prtFII, but not sfbI, sfbII or fbp54, is represented more frequently among invasive-disease isolates of tropical Australia.

Streptococcus pyogenes (group A streptococcus) strains may express several distinct fibronectin-binding proteins (FBPs) which are considered as major streptococcal adhesins. Of the FBPs, SfbI was shown in vitro to promote internalization of the bacterium into host cells and has been implicated in persistence. In the tropical Northern Territory, where group 4 streptococcal infection is common, multiple genotypes of the organism were found among isolates from invasive disease cases and no dominant strains were observed. To determine whether any FBPs is associated with invasive disease propensity of S. pyogenes, we have screened streptococcal isolates from bacteraemic and necrotizing fasciitis patients and isolates from uncomplicated infections for genetic endowment of 4 FBPs. No difference was observed in the distribution of sfbII, fbp54 and sfbI between the blood isolates and isolates from uncomplicated infection. We conclude that the presence of sfbI does not appear to promote invasive diseases, despite its association with persistence. We also show a higher proportion of group A streptococcus strains isolated from invasive disease cases possess prtFII when compared to strains isolated from non-invasive disease cases. We suggest that S. pyogenes may recruit different FBPs for different purposes.

Adhesins, Bacterial↗

An audit of the use of granulocyte colony-stimulating factor in septic shock.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) stimulates the production of neutrophils and modulates the function and activity of developing and mature neutrophils. In septic shock, the immune system can be considered one of the failing organ systems. G-CSF improves immune function and may be a useful adjunctive therapy in patients with septic shock. AIM: To evaluate the introduction of G-CSF as an adjunct to our standard treatment for community-acquired septic shock. METHODS: We performed a prospective data collection and analysis to determine whether the addition of G-CSF to our standard treatment for community-acquired septic shock was associated with improved hospital outcome, compared with an historical cohort of similar patients. We included all patients admitted to the Intensive Care Unit (ICU) with community-acquired septic shock between December 1998 and March 2000. Patients received 300 microg G-CSF intravenously daily for 10 days in addition to our standard treatment for community-acquired septic shock. G-CSF was discontinued early if the patient was discharged from ICU before 10 days or if the absolute neutrophil count exceeded 75 x 10(6)/mL. RESULTS: A total of 36 patients with community-acquired septic shock, an average Apache 2 score of 26.7, and a predicted mortality of 0.79, were treated with G-CSF from December 1998 to March 2000. Hospital mortality was 31% compared with an historical cohort of 11 similar patients with a hospital mortality of 73% (P = 0.018). In the subgroup of patients with melioidosis septic shock, the hospital survival improved from 5% to 100% (P < 0.0001). No significant adverse events occurred as a result of the administration of G-CSF. CONCLUSION: G-CSF is a safe adjunctive therapy in community-acquired septic shock and may be associated with improved outcome. The use of G-CSF in septic shock should undergo further investigation to define subgroups of patients who may benefit from G-CSF. The use of G-CSF in patients with septic shock due to Burkholderia pseudomallei is recommended.

Adolescent↗

Outcome of an interventional program for scabies in an Indigenous community.

OBJECTIVE: To implement an intervention program for reducing the prevalence of scabies in a large Northern Territory Aboriginal community. DESIGN: Prospective, longitudinal screening, intervention and follow-up study. PARTICIPANTS AND SETTING: All children aged 5 years and under in one of the largest Aboriginal communities in the Northern Territory, total population, approximately 2,200 (95% Indigenous). MAIN OUTCOME MEASURES: A decrease in prevalence of scabies, infected scabies and non-scabies pyoderma over seven months. RESULTS: The number of children aged 5 years and under screened intially and at the three follow-up screenings ranged from 201 to 242 (more than 98% of those eligible on each occasion). The prevalences of scabies, infected scabies and non-scabies pyoderma before intervention were 35%, 12% and 11%, respectively. At 6 weeks postintervention these had decreased to 3%, 1% and 4%, respectively; low prevalences were maintained at four and seven months. CONCLUSIONS: This intervention, which was based on community motivation, involvement and control, successfully reduced the prevalence of scabies. Continuing community health education and regular screening will be crucial in controlling scabies. The methods and results of this study may be helpful in developing a coordinated program for all remote Aboriginal communities in the area.

Australia↗

Clinical effects of bites from formally identified spiders in tropical Northern Territory.

OBJECTIVE: To determine the types of spiders causing bites and the clinical effects of their bites in tropical Northern Territory (north of the town of Katherine). DESIGN: A prospective study of confirmed and suspected spider-bites and a retrospective analysis of data from a standardised, local database of spider- and snake-bites. Confirmed spider-bites were those in which there was a clear history of the bite, and the captured spider was identified by an arachnologist. SETTING: Emergency department of a teaching hospital. SUBJECTS AND DATA SOURCE: All subjects with confirmed or suspected spider-bite presenting to the Emergency Department or referred from August 1999 to August 2000, or identified from the database. RESULTS: Thirty-four subjects had a confirmed spider-bite from an identified spider: 25 in the prospective group and nine in the retrospective group. The spiders were Sparassidae (huntsman spider) (12 bites), Missulena pruinosa (northern mouse spider) (7), Latrodectus (widow spider) (4), Araneidae (orb-weaver) (4), Salticidae (jumping spider) (4), Nemesidae (trapdoor spider) (1), Conothele (1) and Selenocosmia (whistling spider) (1). Clinical effects were local pain in 97% (severe in 29%), redness in 47% and swelling in 24% of cases. Systemic effects occurred in three victims, two of whom were bitten by M. pruinosa. There were no cases of confirmed necrotic arachnidism. CONCLUSIONS: None of the spider-bites resulted in severe effects. Compared with data from other parts of Australia, different species were involved and latrodectism was uncommon. Our study highlighted the importance of correctly identifying the spider species.

Adolescent↗

Antibiotic susceptibility of Burkholderia pseudomallei from tropical northern Australia and implications for therapy of melioidosis.

From a prospective melioidosis study commencing in 1989 at Royal Darwin Hospital, 170 initial isolates of Burkholderia pseudomallei were available for susceptibility testing. Of these 163 (96%) were susceptible to meropenem/imipenem, ceftazidime, trimethoprim-sulphamethoxazole (SMX/TMP) and doxycycline. Seven (4%) showed primary resistance; three had low-level resistance to SMX/TMP, one to ceftriaxone and amoxycillin/clavulanate (AMOX/CA) and three to doxycycline. Of 167 patients who survived their initial presentation, seven (4%) had culture positive infections which persisted for greater than 3 months after start of therapy. All ultimately cleared carriage of B. pseudomallei though three required changing to SMX/TMP after development of doxycycline resistance. Nineteen (11%) of the initial survivors clinically relapsed and 17 of these had repeat isolates available for testing. Four of these had acquired resistance: one to doxycycline, one to AMOX/CA and ceftazidime, one to SMX/TMP and one to both SMX/TMP and doxycycline. Molecular typing using randomly amplified polymorphic DNA and pulsed-field gel electrophoresis showed all but one relapse isolate to be the same as the original strain. These data are similar to published data from Thailand. As melioidosis has a high mortality (21% in this series) these results emphasize the need for prolonged eradication therapy and regular clinical and microbiological monitoring so that the emergence of resistance can be detected early and appropriate treatment modifications made.

Amoxicillin-Potassium Clavulanate Combination↗

Burkholderia pseudomallei virulence: definition, stability and association with clonality.

Clinical presentations of melioidosis, caused by Burkholderia pseudomallei are protean, but the mechanisms underlying development of the different forms of disease remain poorly understood. In murine melioidosis, the level of virulence of B. pseudomallei is important in disease pathogenesis and progression. In this study, we used B. pseudomallei-susceptible BALB/c mice to determine the virulence of a library of clinical and environmental B. pseudomallei isolates from Australia and Papua New Guinea. Among 42 non-arabinose-assimilating (ara(-)) isolates, LD(50) ranged from 10 to > 10(6) CFU. There were numerous correlations between virulence and disease presentation in patients; however, this was not a consistent observation. Virulence did not correlate with isolate origin (i.e. clinical vs environmental), since numerous ara(-) environmental isolates were highly virulent. The least virulent isolate was a soil isolate from Papua New Guinea, which was arabinose assimilating (ara(+)). Stability of B. pseudomallei virulence was investigated by in vivo passage of isolates through mice and repetitive in vitro subculture. Virulence increased following in vivo exposure in only one of eight isolates tested. In vitro subculture on ferric citrate-containing medium caused attenuation of virulence, and this correlated with changes in colony morphology. Pulsed-field gel electrophoresis and randomly amplified polymorphic DNA typing demonstrated that selected epidemiologically related isolates that had variable clinical outcomes and different in vivo virulence were clonal strains. No molecular changes were observed in isolates after in vivo or in vitro exposure despite changes in virulence. These results indicate that virulence of selected B. pseudomallei isolates is variable, being dependent on factors such as iron bioavailability. They also support the importance of other variables such as inoculum size and host risk factors in determining the clinical severity of melioidosis.

Animals↗

Paediatric melioidosis in the Northern Territory of Australia: an expanding clinical spectrum.

OBJECTIVE: The objective of this study was to present the laboratory and clinical features of the six cases of paediatric melioidosis diagnosed from 1997-2000. METHODOLOGY: All cases of melioidosis confirmed by the pathology department of Royal Darwin Hospital were prospectively identified by culture and/or serology. RESULTS: Four children were Aboriginal and all six cases presented during the rainy season (November-April) in rural areas in the tropical Top End of the Northern Territory. Delay in diagnosis ranged from 5 and 11 days. Two cases had localized melioidosis, two cases had underlying disease and were likely to be colonized with Burkholderia pseudomallei (B. pseudomallei). Two cases had neurological melioidosis with major residual disability. No deaths occurred. CONCLUSIONS: Melioidosis remains an unusual disease in children in the tropical Northern Territory. The average annual incidence since 1997 is 5.48 per 100 000. This series demonstrates that children in Australia can have serious neurological complications from B. pseudomallei infection. All children living in or visiting tropical Australia are at risk, especially those residing in rural areas in the rainy season. Melioidosis remains a difficult disease to manage, and expert opinion should be sought if B. pseudomallei is cultured from any site.

Child↗

Childhood infections in the tropical north of Australia.

In the tropical north of Australia there are high rates of infections in Aboriginal children living in remote communities. In addition to the burden of respiratory infections, diarrhoeal disease and skin sepsis, there are high rates of acute rheumatic fever, outbreaks of poststreptococcal glomerulonephritis and gonococcal conjunctivitis, endemic trachoma and various intestinal parasites. A number of infections generally restricted to the tropics are also present and can cause disease in both indigenous and non-indigenous children. These include melioidosis, Murray Valley encephalitis and dengue on the east coast. With global warming, these infections may become more common and more widespread within Australia and the potential for establishment of introduced infections such as Japanese encephalitis and malaria may increase.

Adolescent↗

Paraplegia secondary to Burkholderia pseudomallei myelitis: a case report.

Bacterial infection is an uncommon cause of acute paraplegia. A 42-year-old Aboriginal man presented to a remote health clinic in northern Australia with myelitis associated with Burkholderia pseudomallei. He was treated with analgesia and intravenous flucloxacillin, ceftriaxone, and gentamicin and transferred to our hospital, where an urgent T12-L1 laminectomy and decompression was performed. Urine culture confirmed B. pseudomallei infection (melioidosis). Abdominopelvic computed tomography revealed left prostatic lobe and right periprostatic abscesses, which were managed conservatively. The patient was given intravenous ceftazidime (8g/d) for 2 months, followed by oral sulfamethoxazole (1600mg) and trimethoprim (320mg) twice daily for 8 weeks. Magnetic resonance imaging 3 weeks after his admission confirmed transverse myelitis. His rehabilitation was complicated by his difficulty in adjusting to disability, by urinary retention and fecal incontinence, by communication barriers, and his isolation from a culture familiar to him. He returned to his community after 15 weeks, free of infection, with T10-11 paraplegia and an indwelling catheter.

Adult↗

Persistent ICT malaria P.f/P.v panmalarial and HRP2 antigen reactivity after treatment of Plasmodium falciparum malaria is associated with gametocytemia and results in false-positive diagnoses of Plasmodium vivax in convalescence.

A problem with rapid Plasmodium falciparum-specific antigen histidine-rich protein 2 (HRP2) detection tests for malaria is the persistence of antigen in blood after the disappearance of asexual-stage parasitemia and clinical symptoms, resulting in false-positive (FP) test results following treatment. The ICT P.f/P.v immunochromatographic test detects both HRP2 and a panmalarial antigen (PMA) found in both P. falciparum and Plasmodium vivax. To examine posttreatment antigen persistence with this test and whether persistent sexual-stage forms (gametocytes) are a cause of FP tests after treatment, we compared serial antigen test results with microscopy results from patients symptomatic with P. falciparum malaria in Indonesia for 28 days following treatment with chloroquine (CQ; n = 66), sulfadoxine-pyrimethamine (SP; n = 36), and artesunate plus sulfadoxine-pyrimethamine (ART + SP; n = 15). Persistent FP antigenemia following SP treatment occurred in 29% (HRP2) and 42% (PMA) of the patients on day 7 and in 10% (HRP2) and 23% (PMA) on day 14. The high rates of persistent HRP2 and PMA antigenemia following CQ and SP treatment were strongly associated with the presence of gametocytemia, with the proportion with gametocytes on day 7 posttreatment being significantly greater in those with FP results than in those with true-negative PMA and HRP2 results. Gametocyte frequency on day 14 post-SP treatment was also greater in those with FP PMA results. Following SP treatment, PMA persisted longer than HRP2, giving an FP diagnosis of P. vivax in up to 16% of patients on day 14, with all FP P. vivax diagnoses having gametocytemia. In contrast, PMA was rapidly cleared following ART + SP treatment in association with rapid clearance of gametocytemia. Gametocytes appear to be an important cause of persistent posttreatment panmalarial antigenemia in areas of endemicity and may also contribute in part to persistent HRP2 antigenemia following treatment.

Adult↗

Rheumatic fever in a high incidence population: the importance of monoarthritis and low grade fever.

AIMS: To describe the clinical features of rheumatic fever and to assess the Jones criteria in a population and setting similar to that in many developing countries. METHODS: The charts of 555 cases of confirmed acute rheumatic fever in 367 patients (97% Aboriginal) and more than 200 possible rheumatic fever cases from the tropical "Top End" of Australia's Northern Territory were reviewed retrospectively. RESULTS: Most clinical features were similar to classic descriptions. However, monoarthritis occurred in 17% of confirmed non-chorea cases and 35% of unconfirmed cases, including up to 27 in whom the diagnosis was missed because monoarthritis is not a major manifestation. Only 71% and 25% of confirmed non-chorea cases would have had fever using cut off values of 38 degrees C and 39 degrees C, respectively. In 17% of confirmed non-chorea cases, anti-DNase B titres were raised but antistreptolysin O titres were normal. Although features of recurrences tended to correlate with initial episodes, there were numerous exceptions. CONCLUSIONS: Monoarthritis and low grade fever are important manifestations of rheumatic fever in this population. Streptococcal serology results may support a possible role for pyoderma in rheumatic fever pathogenesis. When recurrences of rheumatic fever are common, the absence of carditis at the first episode does not reliably predict the absence of carditis with recurrences.

Adolescent↗