Now showing 1 - 10 of 476
  • 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
    Journal Article
    The impact of delayed treatment of uncomplicated P. falciparum malaria on progression to severe malaria: A systematic review and a pooled multicentre individual-patient meta-analysis.
    (2020-10-19)
    Mousa A
    ;
    Al-Taiar A
    ;
    ;
    Badaut C
    ;
    Barber BE
    ;
    Bassat Q
    ;
    Challenger JD
    ;
    Cunnington AJ
    ;
    Datta D
    ;
    Drakeley CJ
    ;
    Ghani AC
    ;
    Gordeuk VR
    ;
    Grigg MJ
    ;
    Hugo P
    ;
    John CC
    ;
    Mayor A
    ;
    Migot-Nabias F
    ;
    Opoka RO
    ;
    Pasvol G
    ;
    Rees C
    ;
    Reyburn H
    ;
    Riley EM
    ;
    Shah BN
    ;
    Sitoe A
    ;
    Sutherland CJ
    ;
    Thuma PE
    ;
    Unger SA
    ;
    Viwami F
    ;
    Walther M
    ;
    Whitty CJM
    ;
    William T
    ;
    Okell LC
    BACKGROUND: Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as 'test-and-treat' policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM. METHODS AND FINDINGS: A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case-control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle-Ottawa scale, and all studies were ranked as 'Good', scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged <15 years) SM patients and 5,780 (79.6% aged <15 years) UM cases in Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda, Yemen, and Zambia. Definitions of SM were standardised across studies to compare treatment delay in patients with UM and different SM phenotypes using age-adjusted mixed-effects regression. The odds of any SM phenotype were significantly higher in children with longer delays between initial symptoms and arrival at the health facility (odds ratio [OR] = 1.33, 95% CI: 1.07-1.64 for a delay of >24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92-4.06; p < 0.001) for a delay of 2-3 days and 5.46 (95% CI: 3.49-8.53; p < 0.001) for a delay of >7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR [95% CI] >3 to ≤4 days versus ≤24 hours: cerebral malaria [CM] = 2.42 [1.24-4.72], p = 0.01; respiratory distress syndrome [RDS] = 4.09 [1.70-9.82], p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify. CONCLUSIONS: Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment.
      1300
  • 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
    Severe Disseminated Gonococcal Infection with Polyarticular Gout: Two Cases in Older Travelers.
    (2018-11-19)
    Smith EL
    ;
    Hodgetts KE
    ;
    ;
    Two male travelers with histories of gout and hazardous alcohol consumption, presented with a triad of severe culture-positive disseminated gonococcal infection, crystal-positive polyarticular gout, and gonococcal soft tissue collections, following unprotected sexual contact in The Philippines. Both men initially attributed symptoms to gout, since their usual joints were affected, but clinical deterioration occurred with self-administration of anti-inflammatory agents alone. The clinical courses were severe and protracted, requiring aggressive management of infection with prolonged intravenous antimicrobials and repeated surgery, and prolonged anti-inflammatory agents for gout. Joint symptom onset in each case occurred within a week of sexual exposure in conjunction with hazardous alcohol ingestion. We speculate that acute dissemination of infection to previously damaged joints triggered polyarticular gout, with progressive infection, exacerbated by unopposed anti-inflammatory agents and delayed antibiotics. Disseminated gonococcal infection can occur with polyarticular gout and delays in recognition and treatment, including while traveling, can lead to severe disease from both.
      1285
  • 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
    Age-Related Clinical Spectrum of Plasmodium knowlesi Malaria and Predictors of Severity.
    (2018-07-18)
    Grigg MJ
    ;
    William T
    ;
    Barber BE
    ;
    Rajahram GS
    ;
    Menon J
    ;
    Schimann E
    ;
    Piera K
    ;
    Wilkes CS
    ;
    Patel K
    ;
    Chandna A
    ;
    Drakeley CJ
    ;
    Yeo TW
    ;
    Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only Plasmodium species are lacking. Over 3.5 years, we prospectively assessed patients of any age with molecularly-confirmed Plasmodium monoinfection presenting to 3 district hospitals in Sabah, Malaysia. Of 481 knowlesi, 172 vivax, and 96 falciparum malaria cases enrolled, 44 (9%), 71 (41%), and 31 (32%) children aged ≤12 years. Median parasitemia was lower in knowlesi malaria (2480/μL [interquartile range, 538-8481/μL]) than in falciparum (9600/μL; P < .001) and vivax malaria. In P. knowlesi, World Health Organization-defined anemia was present in 82% (95% confidence interval [CI], 67%-92%) of children vs 36% (95% CI, 31%-41%) of adults. Severe knowlesi malaria occurred in 6.4% (95% CI, 3.9%-8.3%) of adults but not in children; the commenst severity criterion was acute kideny injury. No patient had coma. Age, parasitemia, schizont proportion, abdominal pain, and dyspnea were independently associated with severe knowlesi malaria, with parasitemia >15000/μL the best predictor (adjusted odds ratio, 16.1; negative predictive value, 98.5%; P < .001). Two knowlesi-related adult deaths occurred (fatality rate: 4.2/1000 adults). Age distribution and parasitemia differed markedly in knowlesi malaria compared to human-only species, with both uncomplicated and severe disease occurring at low parasitemia. Severe knowlesi malaria occurred only in adults; however, anemia was more common in children despite lower parasitemia. Parasitemia independently predicted knowlesi disease severity: Intravenous artesunate is warranted initially for those with parasitemia >15000/μL.
      1351
  • 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