Now showing 1 - 10 of 292
  • Publication
    Journal Article
    Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis.
    (2023-02-08)
    Settles EW
    ;
    Sonderegger D
    ;
    Shannon AB
    ;
    Celona KR
    ;
    Lederer R
    ;
    Yi J
    ;
    Seavey C
    ;
    Headley K
    ;
    Mbegbu M
    ;
    Harvey M
    ;
    Keener M
    ;
    Allender C
    ;
    Hornstra H
    ;
    Monroy FP
    ;
    Woerle C
    ;
    Theobald, Vanessa
    ;
    Mayo M
    ;
    ;
    Keim P
    Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative soil bacterium well recognized in Southeast Asia and northern Australia. However, wider and expanding global distribution of B. pseudomallei has been elucidated. Early diagnosis is critical for commencing the specific therapy required to optimize outcome. Serological testing using the indirect hemagglutination (IHA) antibody assay has long been used to augment diagnosis of melioidosis and to monitor progress. However, cross reactivity and prior exposure may complicate the diagnosis of current clinical disease (melioidosis). The goal of our study was to develop and initially evaluate a serology assay (BurkPx) that capitalized upon host response to multiple antigens. Antigens were selected from previous studies for expression/purification and conjugation to microspheres for multiantigen analysis. Selected serum samples from non-melioidosis controls and serial samples from culture-confirmed melioidosis patients were used to characterize the diagnostic power of individual and combined antigens at two times post admission. Multiple variable models were developed to evaluate multivariate antigen reactivity, identify important antigens, and determine sensitivity and specificity for the diagnosis of melioidosis. The final multiplex assay had a diagnostic sensitivity of 90% and specificity of 93%, which was superior to any single antigen in side-by-side comparisons. The sensitivity of the assay started at >85% for the initial serum sample after admission and increased to 94% 21 days later. Weighting antigen contribution to each model indicated that certain antigen contributed to diagnosis more than others, which suggests that the number of antigens in the assay can be decreased. In summation, the BurkPx assay can facilitate the diagnosis of melioidosis and potentially improve on currently available serology assays. Further evaluation is now required in both melioidosis-endemic and non-endemic settings.
  • Publication
    Journal Article
    Melioidosis.
    (2018-02-01)
    Wiersinga WJ
    ;
    Virk HS
    ;
    Torres AG
    ;
    ;
    Peacock SJ
    ;
    Dance DAB
    ;
    Limmathurotsakul D
    Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.
      670
  • Publication
    Comment
    Petrol sniffer's encephalopathy.
    (1994-06-20) ;
    Burrow J
    ;
    Fisher D
    ;
    Howard D
    ;
    McElver M
    ;
    Burns C
      653
  • Publication
    Journal Article
    Treatment of snakebite in Australia: the current evidence base and questions requiring collaborative multicentre prospective studies.
    (2006-12-01)
    Despite the wealth of anecdotes and case reports there are fundamental questions of management of snakebite in Australia that remain unresolved or for which the current evidence is limited. The efficacy in the field, potential limitations and possibility of improvements in pressure immobilisation first aid need objective studies in humans. Optimal bandage sizes, stretch and pressure for different sized limbs need further evaluation, as does the use of pressure pads. Better definitions of specific clinical envenoming syndromes attributable to individual snake species are required, including elucidation of within-genus variations, similarities and differences. Venom studies suggest this is especially important for species within the brown snake (Pseudonaja) and death adder (Acanthophis) genera. Appropriate antivenom types, doses and dosing intervals for individual snake species should be more formally studied in patients. Especially important are confirmation of the need for higher doses of brown snake antivenom, while possibly limiting unnecessarily high doses, confirmation of the critical importance of early antivenom use to prevent pre-synaptic neurotoxicity in Taipan and tiger snake bites and ascertainment of whether larger doses of antivenom are unhelpful in Taipan bites after specified time delays. Confirmation of clinical efficacy and dosing recommendations for use of tiger snake (Notechis) antivenom in envenoming from Australian copperhead (Austrelaps spp.), broad headed (Hoplocephalus spp.) and rough-scaled snakes (Tropidechis carinatus) also require formal study in patients. Other examples of clinical relevance of cross-specificity of current and future monospecific antivenoms and whether there are geographical variations in antivenom responses within species will require elucidation. Prospective multicentre collaborative studies with predefined data collection and serial venom level assays are proposed as the way forward in Australia to help resolve therapeutic uncertainties and to establish a firmer evidence base for best-practice treatment guidelines for Australasian elapid snakebite.
      1290
  • Publication
    Case Reports
    Scrub typhus in the Northern Territory: exceeding the boundaries of Litchfield National Park.
    (2004) ;
    Raines M
    ;
    Whelan PI
    ;
    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.
      1192
  • Publication
    Journal Article
    Epidemiology of community-acquired and nosocomial bloodstream infections in tropical Australia: a 12-month prospective study.
    (2004-07)
    Douglas MW
    ;
    Lum G
    ;
    Roy J
    ;
    Fisher DA
    ;
    ;
    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%). A 12-month prospective study of blood stream infections in 2000 at Royal Darwin Hospital in the tropical north of Australia. 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. 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.
      1221
  • Publication
    Journal Article
    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.
    (2001-09) ;
    Mayo MJ
    ;
    ;
    Donohoe P
    ;
    Haase A
    ;
    Kemp DJ
    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.
      2847
  • Publication
    Journal Article
    Ivermectin for Sarcoptes scabiei hyperinfestation.
    (1998-01)
    Huffam SE
    ;
    Crusted (Norwegian) scabies is an unusual variant of scabies caused by hyperinfestation with Sarcoptes scabiei. It has high morbidity, and secondary bacterial skin sepsis may result in life-threatening bacteremia. An open label study of oral ivermectin was carried out in patients with crusted scabies refractory to topical therapy. Patients with refractory crusted scabies were prescribed oral ivermectin, one to three doses of 200 mg/kg at 14-day intervals, combined with topical scabicide and keratolytic therapy. Of the 20 patients who received ivermectin, 8 had a complete initial clinical response, a partial response was achieved in 9, and minimal improvement occurred in 3. Three doses of ivermectin were curative for 8 of 10 cases, but recurrence of scabies from presumed reinfestation occurred in at least half of these. The authors conclude that ivermectin is effective for crusted scabies; however, multiple doses may be required to achieve a cure, and recurrence 6 or more weeks after completing treatment is common.
      1292
  • Publication
    Journal Article
    A 16-year prospective study of community-onset bacteremic Acinetobacter pneumonia: low mortality with appropriate initial empirical antibiotic protocols.
    (2014-10)
    Davis JS
    ;
    McMillan M
    ;
    Swaminathan A
    ;
    Kelly JA
    ;
    Piera KE
    ;
    ; ;
    The genus Acinetobacter, well known as a nosocomial pathogen, can also cause severe community-onset pneumonia. Previous small case series have suggested fulminant disease and a pooled hospital mortality of > 60%. We conducted a prospective observational study of all episodes of bacteremic, community-onset, and radiologically confirmed pneumonia due to Acinetobacter species at a tertiary referral hospital in tropical Australia from 1997 to 2012 following the introduction of routine empirical treatment protocols covering Acinetobacter. Demographic, clinical, microbiologic, and outcome data were collected. There were 41 episodes of bacteremic community-onset Acinetobacter pneumonia, of which 36 had no indicators suggesting health-care-associated infection. Of these, 38 (93%) were Indigenous Australians, one-half were men, the average age was 44.1 years, and 36 episodes (88%) occurred during the rainy season. All patients had at least one risk factor, with hazardous alcohol intake in 82%. Of the 37 isolates available for molecular speciation, 35 were Acinetobacter baumannii and two were Acinetobacter nosocomialis. All isolates were susceptible in vitro to gentamicin, meropenem, and ciprofloxacin, but only one was fully susceptible to ceftriaxone. ICU admission was required in 80%. All 41 patients received appropriate antibiotics within the first 24 h of admission, and 28- and 90-day mortality were both low at 11%. Community-acquired Acinetobacter pneumonia is a severe disease, with the majority of patients requiring ICU admission. Most patients have risk factors, particularly hazardous alcohol use. Despite this severity, correct initial empirical antibiotic therapy in all patients was associated with low mortality.
      16535