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Biomedical subjects

Bart J Currie

Publications and source records attributed to Bart J Currie.

At least 73 records · Page 4Linked to original sources

Acute rheumatic fever: a chink in the chain that links the heart to the throat?

Acute rheumatic fever (ARF) remains a major problem in tropical regions, resource-poor countries, and minority indigenous communities. It has long been thought that group A streptococcal (GAS) pharyngitis alone was responsible for acute rheumatic fever; this belief has been supported by laboratory and epidemiological evidence gathered over more than 60 years, mainly in temperate climates where GAS skin infection is uncommon. GAS strains have been characterised as either rheumatogenic or nephritogenic based on phenotypic and genotypic properties. Primary prevention strategies and vaccine development have long been based on these concepts. The epidemiology of ARF in Aboriginal communities of central and northern Australia challenges this view with reported rates of ARF and rheumatic heart disease (RHD) that are among the highest in the world. GAS throat colonisation is uncommon, however, and symptomatic GAS pharyngitis is rare; pyoderma is the major manifestation of GAS infection. Typical rheumatogenic strains do not occur. Moreover, group C and G streptococci have been shown to exchange key virulence determinants with GAS and are more commonly isolated from the throats of Aboriginal children. We suggest that GAS pyoderma and/or non-GAS infections are driving forces behind ARF in these communities and other high-incidence settings. The question needs to be resolved as a matter of urgency because current approaches to controlling ARF/RHD in Aboriginal communities have clearly been ineffective. New understanding of the pathogenesis of ARF would have an immediate effect on primary prevention strategies and vaccine development.

Acute Disease↗

Out of hospital treatment of patients with melioidosis using ceftazidime in 24 h elastomeric infusors, via peripherally inserted central catheters.

BACKGROUND: In the tropical north of the Northern Territory, Australia, 25-50 patients are admitted to Royal Darwin Hospital (RDH) each year with Burkholderia pseudomallei infection, or melioidosis. Treatment consists of initial intensive therapy with 2-4 weeks of intravenous antibiotics. Clinical improvement may occur early and patients often prefer to be managed out of hospital in the Hospital in the Home (HITH). OBJECTIVES: To evaluate safety and efficacy of HITH management of patients with melioidosis. METHODS: A prospective observational study of our standard management which consists of 24 h infusions of ceftazidime infused through a peripherally inserted central catheter (PICC) line, plus oral sulphamethoxazole trimethoprim. Treatment is administered in the home, which may be in Darwin, regional areas or remote communities, or in a self-care unit located in the hospital grounds. RESULTS: From February 1998 to December 2001 150 patients were admitted to RDH with culture confirmed B. pseudomallei infection. Of these, 73 patients were treated with 24 h infusions of ceftazidime, of which 70 patients were managed by HITH. Complications of treatment include a PICC line complication rate of 10.6/1000 days in situ. Nine patients had relapse or recrudescence of disease, nearly all as a result of poor adherence to subsequent oral eradication therapy, these patients were all re-treated successfully. One patient remains infected with B. pseudomallei. CONCLUSION: This clinical outcome study suggests that out of hospital management of melioidosis with 24 h infusions of ceftazidime via a PICC line is safe and effective.

Adolescent↗

Epidemiology of community-acquired and nosocomial bloodstream infections in tropical Australia: a 12-month prospective study.

OBJECTIVES: To define the relative incidence of organisms causing blood stream infections in a tropical setting with a very low prevalence of human immunodeficiency virus infection (<1%). METHODS: A 12-month prospective study of blood stream infections in 2000 at Royal Darwin Hospital in the tropical north of Australia. RESULTS: Significant isolates were grown from 257 sets of blood cultures. Staphylococcus aureus was the most common isolate overall (28%); 26% of these were methicillin-resistant (MRSA). Escherichia coli was the most common cause of community-acquired bacteraemia. Burkholderia pseudomallei caused 32% of community acquired, bacteraemic pneumonia; 6% of bacteraemias overall. Vancomycin-resistant enterococci were not isolated. Crude mortality rates (13% overall; 9% attributable mortality) were lower than in most comparable studies. CONCLUSIONS: The major difference between these findings and surveys performed elsewhere is the presence of B. pseudomallei as a significant cause of bacteraemic community-acquired pneumonia. Our results demonstrate the effects of local environmental and patient characteristics on the range of organisms causing blood stream infections, and emphasize the important role of local microbiology laboratories in guiding empiric antibiotic therapy.

Adolescent↗

Melioidosis epidemiology and risk factors from a prospective whole-population study in northern Australia.

OBJECTIVES: The aims of this study were to describe the epidemiology of melioidosis in tropical northern Australia and to assess the importance of defined risk factors. METHODS: The data were taken from a 14-year prospective study of 364 cases of melioidosis in the 'Top End' of the Northern Territory. A whole-population logistic regression model was used to estimate the crude and adjusted relative risk (RR) for the defined risk factors. RESULTS: The mean age of the study population was 46.8 years, 264 (72.5%) were male, 178 (49%) were aboriginal Australians and 59 (16.2%) died from melioidosis. Average annual incidence was 19.6 cases per 100 000 population, with an estimated rate of 260 cases per 100,000 diabetics per year. Using a whole-population logistic regression model, the estimated crude and adjusted RR [95% confidence intervals (CI)] for melioidosis were 6.3 (5.1-7.8) and 4.0 (3.2-5.1) for those aged > or = 45 years, 2.3 (1.8-2.9) and 2.4 (1.9-3.0) for males, 2.9 (2.3-3.5) and 3.0 (2.3-4.0) for aboriginal Australians, 21.2 (17.1-26.3) and 13.1 (9.4-18.1) for diabetics, 2.7 (2.2-3.4) and 2.1 (1.6-2.6) for those with excess alcohol consumption, 6.8 (5.4-8.6) and 4.3 (3.4-5.5) for chronic lung disease and 6.7 (4.7-9.6) and 3.2 (2.2-4.8) for chronic renal disease, respectively. CONCLUSIONS: Diabetes, excess alcohol intake, chronic renal disease and chronic lung disease are each independent risk factors for melioidosis. In tropical northern Australia, male sex, aboriginal ethnicity and age of > or = 45 years are also independent predictors for melioidosis. Impaired polymorph function may be critical in the predisposition to melioidosis.

Adolescent↗

Outcomes of patients with melioidosis treated with meropenem.

Melioidosis, an infection due to Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. We reviewed our experience with meropenem in the treatment of severe melioidosis in 63 patients over a 6-year period. Outcomes were similar to those of ceftazidime-treated patients (n = 153) despite a deliberate selection bias to more-unwell patients receiving meropenem. The mortality among meropenem-treated patients was 19%. One patient had a possible drug fever associated with the use of meropenem. We conclude that meropenem (1 g or 25 mg/kg every 8 h intravenously for >/=14 days) is an alternative to ceftazidime and imipenem in the treatment of melioidosis. The use of meropenem may be associated with improved outcomes in patients with severe sepsis associated with melioidosis.

Adolescent↗

Plasminogen binding by group A streptococcal isolates from a region of hyperendemicity for streptococcal skin infection and a high incidence of invasive infection.

Reports of resurgence in invasive group A streptococcal (GAS) infections come mainly from affluent populations with infrequent exposure to GAS. In the Northern Territory (NT) of Australia, high incidence of invasive GAS disease is secondary to endemic skin infection, serotype M1 clones are rare in invasive infection, the diversity and level of exposure to GAS strains are high, and no particular strains dominate. Expression of a plasminogen-binding GAS M-like protein (PAM) has been associated with skin infection in isolates elsewhere (D. Bessen, C. M. Sotir, T. M. Readdy, and S. K. Hollingshead, J. Infect. Dis. 173:896-900, 1996), and subversion of the host plasminogen system by GAS is thought to contribute to invasion in animal models. Here, we describe the relationship between plasminogen-binding capacity of GAS isolates, PAM genotype, and invasive capacity in 29 GAS isolates belonging to 25 distinct strains from the NT. In the presence of fibrinogen and streptokinase, invasive isolates bound more plasminogen than isolates from uncomplicated infections (P < or = 0.004). Only PAM-positive isolates bound substantial levels of plasminogen by a fibrinogen-streptokinase-independent pathway (direct binding). Despite considerable amino acid sequence variation within the A1 repeat region of PAM where the plasminogen-binding domain maps, the critical lysine residue was conserved.

Antigens, Bacterial↗

Isolates of Burkholderia pseudomallei from Northern Australia are distinct by multilocus sequence typing, but strain types do not correlate with clinical presentation.

Melioidosis is the disease caused by the saprophytic organism Burkholderia pseudomallei. Previous studies have suggested some strain tropism and differential virulence. In this study, we defined strains by multilocus sequence typing (MLST) of isolates taken from the Top End of Australia's Northern Territory and compared the results with those of other strains typed worldwide. We specifically sought clinical and geographical correlates of strain types. Among 87 Australian isolates, 48 sequence types were defined. None of the sequence types in this study has been found elsewhere in the world. Strains were distributed widely throughout the region, and the different presentations of disease, including neurological and prostatic infection, were associated with many different strains. There was excellent congruence between pulsed-field gel electrophoresis and MLST, and the two typing methods had a similar level of strain discrimination. The work suggests that host and environmental factors may be more important in determining disease presentation than infecting strain type. It is possible that the distinct but diverse strain types found in this study reflect Australia's geographical isolation over many millions of years.

Bacterial Proteins↗

Further evaluation of a rapid diagnostic test for melioidosis in an area of endemicity.

Immunochromatographic test (ICT) kits for the rapid detection of immunoglobulin G (IgG) and IgM antibodies to Burkholderia pseudomallei were compared to the indirect hemagglutination (IHA) assay. In 138 culture-confirmed melioidosis cases, sensitivities were 80, 77, and 88% for IHA, ICT IgG, and ICT IgM, respectively. In a prospective study of 160 consecutive sera samples sent for melioidosis serology, respective specificities were 91, 90, and 69, positive predictive values were 41, 32, and 18, and negative predictive values were 99, 98, and 100%. ICT IgM kits are unreliable for diagnosis of melioidosis, but ICT IgG kits may be useful for diagnosing travelers presenting with possible melioidosis who return from regions where melioidosis is endemic.

Antibodies, Bacterial↗

Cryptococcus infection in tropical Australia.

Eighteen cases of disease caused by the saprophytic fungi Cryptococcus neoformans and Cryptococcus bacillisporus are described from the Northern Territory of Australia. The majority of infections were with Cryptococcus bacillisporus and in the rural Aboriginal population, often causing pulmonary mass lesions.

Amphotericin B↗

Circulating IgE in patients with ordinary and crusted scabies.

Serum from seven patients with ordinary scabies and six with crusted scabies were screened by immunoblotting for IgE- and IgG-specific proteins in an extract of the mite, Sarcoptes scabiei variety canis. Sera from atopic individuals without sensitivity to house dust mites were used as controls. Serum from all of the patients with crusted scabies showed strong IgE binding to 11-21 and IgG binding to 1-7 scabies proteins. In contrast, three of the seven patients with ordinary scabies showed IgE binding to one to six scabies proteins, and their antibody binding was much weaker. Patients with crusted scabies had serum antibody that reacted with larger molecular weight proteins compared with patients with ordinary scabies. The results of this study indicate that patients with crusted scabies showed a pronounced IgE response to scabies mites, whereas patients with ordinary scabies did not.

Animals↗

Scrub typhus in the Northern Territory: exceeding the boundaries of Litchfield National Park.

Scrub typhus is recognised as an important differential diagnosis of fever, rash and sepsis in patients with a history of travel to Litchfield National Park in the Top End of the Northern Territory. All confirmed scrub typhus cases to date from the Northern Territory have visited the Park, but the presence of similar rainforest pockets elsewhere in the Top End suggested further infectious locations might be identified with increased tourism. We report a case of serologically confirmed Orientia tsutsugamushi infection in a man who had not been within Litchfield Park, but had visited another discrete Top End rainforest area.

Adult↗

C-reactive protein in the diagnosis of melioidosis.

Previous work suggested that C-reactive protein (CRP) may be a useful test in the diagnosis of melioidosis, the infection caused by Burkholderia pseudomallei. We reviewed patients with culture-confirmed melioidosis to define the role of this inflammatory marker in the diagnosis of melioidosis. In 175 patients, we found that the admission CRP level may be normal or only mildly elevated, including patients with severe sepsis, fatal cases, and in relapsed melioidosis. In a multivariate analysis, sepsis and bacteremia were more strongly associated with mortality than CRP. Admission levels of CRP are not a sensitive marker for the presence of melioidosis and a normal level cannot be used to exclude acute, chronic, or relapsed melioidosis in febrile patients in or from endemic regions.

C-Reactive Protein↗

Contamination of hand wash detergent linked to occupationally acquired melioidosis.

Two mechanics working at a garage in tropical northern Australia simultaneously developed upper limb melioidosis ulcers. Both patients had Burkholderia pseudomallei of identical pulsed-field gel electrophoresis (PFGE) type (Spe I). Environmental sampling identified B. pseudomallei in a container of commercial hand wash detergent as the likely source of infection, although there were multiple isolates of different PFGE types to the clinical isolates.

Adult↗

Transmission of Burkholderia pseudomallei via breast milk in northern Australia.

Two cases of maternal to child transmission of melioidosis are reported from Australia's tropical north. One infant died of overwhelming sepsis. Both lactating mothers had mastitis. In 1 case, Burkholderia pseudomallei isolated from breast milk was identical on pulsed-field gel electrophoresis with that in blood and cerebrospinal fluid isolates from the infant.

Adult↗

Adjunctive granulocyte colony-stimulating factor for treatment of septic shock due to melioidosis.

Melioidosis, caused by the intracellular pathogen Burkholderia pseudomallei, is endemic in northern Australia and Southeast Asia. Risk factors for this infection have also been associated with functional neutrophil defects. Because of this, granulocyte colony-stimulating factor (G-CSF) was adopted for use in patients with septic shock due to melioidosis in December 1998. We compared the mortality rates from before and after the introduction of G-CSF therapy at the Royal Darwin Hospital (Darwin, Australia) during the period of 1989-2002. The mortality rate decreased from 95% to 10% after the introduction of G-CSF. Risk factors, the duration of illness before presentation, and the severity of illness were similar in both groups. A smaller decrease in mortality among patients in the intensive care unit who did not have melioidosis was observed, suggesting that other changes in management did not account for the magnitude of the benefit seen. We conclude that G-CSF may have contributed to the reduction in the mortality rate among patients with septic shock due to melioidosis.

Adolescent↗