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Department of Paediatrics

Soluble Transferrin Receptor in Aboriginal Children with a High Prevalence of Iron Deficiency and Infection

Milk formulas in acute gastroenteritis and malnutrition: a randomised trial

Small bowel intestinal permeability in Australian Aboriginal children

Enteric pathogens, intestinal permeability and nitric oxide production in acute gastroenteritis

Dual sugar permeability testing in diarrheal disease

Rheumatic fever in Aboriginal children

Childhood infections in the tropical north of Australia

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

Intestinal permeability and diarrhoeal disease in Aboriginal Australians

An iron treatment trial in an aboriginal community: improving non-adherence

 

Division of Medicine

Community-acquired pneumonia in northern Australia: low mortality in a tropical region using locally-developed treatment guidelines

The Bali bombings of 12 October, 2002: lessons in disaster management for physicians

Ubiquity of putative type III secretion genes among clinical and environmental Burkholderia pseudomallei isolates in Northern Australia

Saccade and cognitive function in chronic kava users

Management of chronic hepatitis B virus infection in remote-dwelling Aboriginals and Torres Strait Islanders: an update for primary healthcare providers

Generation and characterization of cDNA clones from Sarcoptes scabiei var. hominis for an expressed sequence tag library: identification of homologues of house dust mite allergens

Identification of a homologue of a house dust mite allergen in a cDNA library from Sarcoptes scabiei var hominis and evaluation of its vaccine potential in a rabbit/S. scabiei var. canis model

Cystic Fibrosis and Burkholderia pseudomallei Infection: An Emerging Problem?

Endemic invasive amoebiasis in northern Australia

Factors supporting sustainability of a community-based scabies control program

HIV-1 infection in foreign nationals working in East Timor

Evidence-based medicine and clinical practice

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

Pulmonary manifestations of uncomplicated falciparum and vivax malaria: cough, small airways obstruction, impaired gas transfer, and increased pulmonary phagocytic activity

Impact of single dose azithromycin on group A streptococci in the upper respiratory tract and skin of Aboriginal children

Community-acquired bacteremic Acinetobacter pneumonia in tropical Australia is caused by diverse strains of Acinetobacter baumannii, with carriage in the throat in at-risk groups

Paraplegia secondary to Burkholderia pseudomallei myelitis: a case report

Retrospective review of febrile neutropenia in the Royal Darwin Hospital, 1994-99

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

Neurological melioidosis

Evaluation of a telemedicine link between Darwin and Adelaide to facilitate cancer management

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Division of Surgery

 

A Unique Pattern of Urinary Tract Calculi in Australian Aboriginal Children

Flipped out of control: single-vehicle rollover accidents in the Northern Territory

Evaluation of amylase and lipase in the diagnosis of acute pancreatitis

Risks to feet in the Top End: outcomes of diabetic foot complications

 

Division of Critical Care

 

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

Prospective study of jellyfish stings from tropical Australia, including the major box jellyfish Chironex fleckeri

Emergency department triage of indigenous and non-indigenous patients in tropical Australia

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

 

Department of Pathology

Clinical value of repeat Pap smear at the time of colposcopy

Studies of measles viruses circulating in Australia between 1999 and 2001 reveals a new genotype

Does cleansing the birth canal at delivery reduce postnatal infection rates?

Surveillance of antibiotic resistance in invasive isolates of Neisseria meningitidis in Australia 1994-1999

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

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

 

 


Department of Paediatrics

 

Soluble Transferrin Receptor in Aboriginal Children with a High Prevalence of Iron Deficiency and Infection

Ritchie B, McNeil Y, Brewster DR

Northern Territory Clinical School, Flinders University and Paediatric Department, Royal Darwin Hospital, Australia.

Abstract: Objectives: Aboriginal children in tropical Australia have a high prevalence of both iron deficiency and acute infections, making it difficult to differentiate their relative contribution to anaemia. The aims of this study were to compare soluble transferrin receptor with ferritin in iron deficiency anaemia, and to examine how best to distinguish the effect of iron deficiency from infection on anaemia. Methods: We carried out a prospective study of 228 admissions to Royal Darwin Hospital in children from 6 to 60 months of age. Transferrin receptor concentrations were measured by a particle enhanced immunoturbidimetric assay and ferritin by a microparticle enzyme immunoassay. Results: On multiple regression, the best explanatory variables for haemoglobin differences (r2=33.7%, p<0.001) were mean corpuscular volume (MCV), red cell distribution width (RDW) and C-reactive protein (CRP), with transferrin receptor and ferritin not significant (p>0.4). Using =2 abnormal indices (MCV, RDW, blood film) + haemoglobin <110g/L as the reference standard for iron deficiency anaemia, transferrin receptor produced a higher area under the curve on ROC curve analysis than ferritin (0.76 vs 0.61, p<0.001) or the transferrin receptor-ferritin index (0.74). On logistic regression, the effect of acute infection (CRP) on haemoglobin was significant (p<0.001) at cut-offs of 105 and 110g/L, but not at 100g/L. Conclusions: Transferrin receptor does not significantly improve the diagnosis of anaemia (iron deficiency vs infection) over full blood count and CRP, but in settings with a high burden of infectious diseases and iron deficiency, it is a more reliable adjunctive measure of iron status than ferritin.

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Milk formulas in acute gastroenteritis and malnutrition: a randomised trial.

Kukuruzovic RH, Brewster DR.

Northern Territory Clinical School, Flinders University and Paediatric Department, Royal Darwin Hospital, Australia.

J Paediatr Child Health 2002;38:571-7

Abstract: OBJECTIVE: To compare three low-lactose milk formulas differing in osmolality and degree of protein hydrolysis in the treatment of diarrhoea and malnutrition in subjects with high rates of lactose intolerance, osmotic diarrhoea and a tropical/environmental enteropathy. METHODS: A randomised double-blind trial of 180 Aboriginal children under 3 years of age admitted with acute diarrhoea and/or malnutrition was carried out. The intervention milk formulas were: (i) De-Lact, a low-osmolality lactose-free formula; (ii) O-Lac, a lactose-free formula; and (iii) Alfare, a partially hydrolysed formula. Outcome measures were diarrhoeal severity, weight gain, formula palatability and changes in intestinal permeability (L/R ratios). RESULTS: The duration of diarrhoea in days (mean; 95% confidence interval) was significantly longer on Alfare (8.5; 7.0-10.0) compared to De-Lact (6.1; 5.0-7.2) and O-Lac (6.9; 5.6-8.1; P = 0.04). There were no differences in mean intake between formulas, but palatability of Alfare was significantly worse (P < 0.01) than the other formulas. Over the trial 5 days,

improvement in L/R ratios was significantly greater (P = 0.05) for De-Lact (18.6; 10.6-26.6) than for Alfare (8.5; 2.1-14.9). Weight gain was not significantly different between the three formulas, except in a malnourished subgroup who had better weight gain on De-Lact (P = 0.05). CONCLUSIONS: In these Aboriginal children with diarrhoea and growth failure, a low osmolality milk was associated with better outcomes and a partially hydrolysed formula with less improvement in mucosal recovery, suggesting that cow's milk protein intolerance is not contributing to greater diarrhoeal severity or enteropathy in Aboriginal children.

 

Small bowel intestinal permeability in Australian Aboriginal children.

Kukuruzovic RH, Brewster DR.

NT Clinical School, Flinders University and Paediatric Department, Royal Darwin Hospital.

J Pediatr Gastroenterol Nutr 2002;35:206-12

Abstract: OBJECTIVE: To show that the severity of diarrheal disease in Aboriginal children in tropical Australia is a consequence of underlying small intestinal mucosal damage. STUDY DESIGN: A prospective study of 338 Aboriginal admissions compared to 37 non-Aboriginal children, both diarrhea cases and controls. Intestinal permeability was measured by lactulose-rhamnose (L/R) ratios on a timed 90-minute blood test. RESULTS: For diarrheal admissions, significantly more Aboriginal (vs. non-Aboriginal children) had hypokalemia (70 vs. 10%), acidosis (65 vs. 29%), moderate to severe dehydration (52 vs. 19%) and a longer mean length of stay (mean 8.9 vs. 3.9 days). Mean L/R ratios (95% confidence intervals) in Aboriginal children (diarrhea vs. controls) were 16.5 (14.6-18.7) vs. 4.5 (3.8-5.3) compared to 7.7 (4.4-13.3) vs. 2.5 (1.8-3.4), respectively, in non-Aboriginals. Abnormal permeability ratios (> 5.6) consistent with tropical-environmental enteropathy syndrome were found in 36% (27/75) of Aboriginal controls compared to none of the non-Aboriginal controls. On multiple regression, the factors associated with high L/R ratios were diarrheal severity ( < 0.001), acidosis ( = 0.007) and hypokalemia ( = 0.04). CONCLUSIONS: An underlying tropical-environmental enteropathy contributes to the severity of acute gastroenteritis in Aboriginal children. Diarrheal complications, such as acidosis, hypokalemia, and osmotic diarrhea are associated with high L/R ratios, reflecting greater small intestinal mucosal damage.

 

Enteric pathogens, intestinal permeability and nitric oxide production in acute gastroenteritis.

Kukuruzovic R, Robins-Browne RM, Anstey NM, Brewster DR.

Northern Territory Clinical School, Flinders University, c/o Royal Darwin Hospital, Australia.

Pediatr Infect Dis J 2002;21:730-9

Abstract: BACKGROUND: Aboriginal children hospitalised with diarrheal disease in northern Australia have high rates of acidosis, hypokalemia and osmotic diarrhea, as well as abnormal small bowel permeability and elevated nitric oxide (NO) production. METHODS: In a study of 291 diarrheal admissions and 84 controls, we examined the relationship of diarrheal severity outcomes with specific enteric pathogens. NO production was measured by urine nitrate plus nitrite excretion on a low nitrate diet, small bowel permeability by the lactulose:rhamnose ratio on a timed blood specimen and stool pathogens by standard microbiologic investigations and PCR. RESULTS: The addition of diagnostic tests for Escherichia coli to standard stool microbiologic testing increased the rate of specific diagnoses from 53% to 75%, but with multiple pathogens isolated from 34%. The most frequently isolated pathogens from diarrheal patients were enteroaggregative E. coli (28.9%), rotavirus (26.5%), enteropathogenic E. coli (17.2%), Salmonella spp. (10.7%), Cryptosporidium parvum (7.2%) and Strongyloides stercoralis (7.2%). High geometric mean permeability ratios (95% confidence intervals) occurred with rotavirus (19.6; 15.3 to 25.1), enteroaggregative E. coli (21.2; 15.3 to 29.3) and Cryptosporidium (23.0; 15.1 to 35.1) compared with 9.4 (6.8 to 13.1) for no pathogens. NO production was highest for Cryptosporidium (3.7; 2.3 to 6.1) compared with 0.6 (0.4 to 1.1) for no pathogens. Multiple regression analysis revealed significant associations (P < 0.001) for rotavirus with acidosis and osmotic diarrhea, for Strongyloides with wasting and hypokalemia and for Cryptosporidium with severe and prolonged diarrhea. CONCLUSIONS: Cryptosporidium, Strongyloides, rotavirus and enteroaggregative E. coli are important contributors to the severe manifestations of acute gastroenteritis in Australian Aboriginal children.

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Dual sugar permeability testing in diarrheal disease.

Haase AM, Kukuruzovic RH, Dunn K, Bright A, Brewster DR.

NT Clinical School & Royal Darwin Hospital.

J Pediatr 2000;136:232-7

Abstract: OBJECTIVE: To assess the validity of the use of a blood specimen for the sugar permeability test because of the high failure rate of 5-hour urine collection in young children with diarrhea. STUDY DESIGN: Simultaneous 5-hour urine collections and timed blood tests were taken after ingestion of an isotonic solution of lactulose (L) and L-rhamnose (R) in 24 children with acute gastroenteritis and 25 children without diarrhea in a control group. Sugars were measured with high performance liquid chromatography, and the percent of recovered sugars was expressed as an L-R ratio. RESULTS: With acute gastroenteritis the geometric mean L-R ratios (95% confidence intervals) were 12.4 (9.3 to 16.3) in urine and 9.4 (6.7 to 13.1) in blood compared with 6.7 (5.0 to 8.8) and 5.9 (4.4 to 7.8), respectively, in the control group. The level of agreement (kappa) among normal, intermediate, and high ratios for blood and urine was 0.71 (0.51 to 0.92). The failure rate of L-R tests was significantly reduced with a blood specimen (urine 37% vs blood 10%; P <.0001). CONCLUSIONS: Intestinal permeability testing on a blood specimen is a valid alternative to urine collection in young children and has a significantly lower test failure rate.

 

Rheumatic fever in Aboriginal children.

Currie BJ, Brewster DR.

J Paediatr Child Health 2002;38:223-5

 

Childhood infections in the tropical north of Australia.

Currie BJ, Brewster DR.

Northern Territory Clinical School & Royal Darwin Hospital.

J Paediatr Child Health 2001;37:326-30

Abstract: 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.

 

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

Edmond KM, Bauert P, Currie BJ.

Maternal and Child Health Division, Royal Darwin Hospital, Northern Territory, Australia.

J Paediatr Child Health 2001;37:337-41

Abstract: 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.

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Intestinal permeability and diarrhoeal disease in Aboriginal Australians.

Kukuruzovic RH, Haase A, Dunn K, Bright A, Brewster DR.

NHMRC Centre of Clinical Excellence in Aboriginal Health, NT Clinical School, Flinders University and Royal Darwin Hospital, PO Box 41326, Casuarina, Darwin, NT 0811, Australia.

Arch Dis Child 1999;81:304-8

Abstract: BACKGROUND: Northern Territory Aboriginal children hospitalised with acute gastroenteritis have high rates of acidosis, hypokalaemia, and dehydration. AIMS: To determine whether Aboriginal children with and without diarrhoea have greater impairment in intestinal function than non-Aboriginal children, as assessed by increased permeability ratios. METHODS: A descriptive study of 124 children (96 Aboriginal and 28 non-Aboriginal) hospitalised with and without diarrhoea. Intestinal permeability was assessed by the lactulose to rhamnose (L-R) ratio from a five hour urine collection. RESULTS: In Aboriginal children, mean L-R ratios (95% confidence intervals) were 18.3 (17.1 to 19.6) with diarrhoea and 9.0 (7.3 to 11.0) without diarrhoea, and in non-Aboriginal children they were 5.9 (2.8 to 12. 3) and 4.2 (3.3 to 5.2), respectively. In patients with diarrhoea, L-R ratios were significantly raised when accompanied by acidosis (mean, 22.8; 95% CI, 17.0 to 30.5), hypokalaemia (mean, 20.7; 95% CI, 15.4 to 27.9), and >/= 5% dehydration (mean, 24.3; 95% CI, 19.0 to 29.6) compared with none of these complications (mean, 7.0; 95% CI, 3.5 to 13.8). CONCLUSION: The high incidence of acidosis, hypokalaemia, and dehydration in Aboriginal children admitted with diarrhoeal disease is related to underlying small intestinal mucosal damage.

 

An iron treatment trial in an aboriginal community: improving non-adherence.

Kruske SG, Ruben AR, Brewster DR.

Territory Health Services, Northern Territory, Australia.

J Paediatr Child Health 1999;35:153-8

Abstract: OBJECTIVE: To compare supervised vs unsupervised oral iron treatment in anaemic Aboriginal children living in a remote community with a 40% prevalence of iron deficiency anaemia. METHODOLOGY: A randomised unblinded clinical trial in children < 6 years presenting to a remote Health Centre with anaemia. Oral iron prescribed as a daily unsupervised dose (group A) was compared to twice weekly supervised administration (group B) over 12 weeks. Parenteral iron (group C) was reserved for failure of oral treatment. RESULTS: Only 3 of 25 children in group A responded to treatment compared to 23 of 26 children in group B (odds ratio = 7.7, 95% confidence interval 2.6-25.0). After six weeks of treatment, the mean haemoglobin rise was 0.96 g/L in group A compared to 10.9 g/L in group B and 12.4 g/L in group C. On entry to the study, 29.4% of subjects were underweight, 33.3% stunted and 35.3% microcephalic. The mean catch-up in weight/height on iron treatment over the study was only 0.28 (0.08, 0.48) Z-scores. CONCLUSIONS: Oral iron as directly observed twice weekly treatment is superior to unsupervised therapy. In view of the poor compliance with unsupervised treatment and the high prevalence of iron deficiency anaemia (along with stunting and microcephaly) in Aboriginal children in northern Australia, we propose to undertake in partnership with communities a nutritional intervention program with a high energy weaning food fortified with micronutrients (iron, vitamin A, zinc, folate) as the most effective strategy to address these nutritional problems in the weaning period.

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Division of Medicine

Community-acquired pneumonia in northern Australia: low mortality in a tropical region using locally-developed treatment guidelines

Elliott J, Anstey N, Jacups S, Fisher D, Currie B.

International Journal of Infections Diseases 2005; 9: 15-20.

Summary: To investigate the epidemiology and outcome of adult community-acquired pneumonia (CAP) in tropical Australia.

Methods: A prospective study was performed of all adult patients with CAP admitted to the Royal Darwin Hospital, a major hospital in tropical northern Australia.  A standard definition of CAP was used and data collected on demographics, risk factors, history, examination, investigations, treatment and outcome.  Locally-developed treatment guidelines were used.

Results: Once hundred and sixty-seven adults were included in the analysis.  Aboriginal people were over-represented, younger and were more likely to have risk factors for CAP.  The most frequent pathogens isolated were Streptococcus pneumoniae and Burkholderia pseudomallei.  'Atypical pneumonia" organisms were uncommon.  Treatment guidelines included penicillin for mild pneumonia but emphasised coverage of Burkholderia pseudomallei in those with risk factors, especially during the monsoon season.  The mortality rate from pneumonia was low with three deaths in 167 cases (1.8%).

Conclusions: International guidelines for the management of CAP have been based on populations and organisms from temperate regions and may not necessarily be applicable to tropical regions.  guidelines based upon local epidemiology must therefore be developed.  This study illustrates how mortality can be minimised using a process of determining local CAP etiology, developing treatment guidelines and auditing patient management. [full paper...]

 

The Bali bombings of 12 October, 2002: lessons in disaster management for physicians.

Fisher D, Burrow J.

Division of Medicine, Royal Darwin Hospital, Darwin, Northern Territory, Australia.

Intern Med J 2003;33:125-6

 

Ubiquity of putative type III secretion genes among clinical and environmental Burkholderia pseudomallei isolates in Northern Australia.

Smith-Vaughan HC, Gal D, Lawrie PM, Winstanley C, Sriprakash KS, Currie BJ.

University of Queensland, Brisbane, Australia. heidi@menzies.edu.au

J Clin Microbiol 2003;41:883-5

Abstract: Horseradish peroxidase-like type III secretion (TTS1) genes were present in all 116 Northern Australian Burkholderia pseudomallei isolates tested but were not detected in other common environmental Burkholderia species. PCR of TTS1 genes may prove valuable as a diagnostic test.

 

Saccade and cognitive function in chronic kava users.

Cairney S, Clough AR, Maruff P, Collie A, Currie BJ, Currie J.

Neuropsychopharmacology 2003;28:389-96

Abstract: Kava is an extract from the Piper methysticum Forst. f. plant that has been consumed in the Pacific islands for millennia and more recently, among indigenous populations, in northern Australia and throughout the Western world as an herbal medicine. Through alterations on neuronal excitation, kava induces muscle relaxation, anaesthesia, and has anxiolytic properties. There have been several isolated reports of psychotic syndromes, severe choreoathetosis and possible seizures following kava use. However, there is no conclusive evidence that kava interferes with normal cognitive processes. We tested a group of current, ex, and non-kava users among an indigenous population in northern Australia, using saccade and cognitive tests that have proven cross-cultural validity and are sensitive to subtle disruptions of the brain arising from substance abuse or neuropsychiatric illness. Despite collecting data from among the heaviest reported kava drinkers in the world, we found no impairment in cognitive or saccade function in individuals who were currently heavy kava users (and had been for up to 18 years), nor was there any impairment in individuals who had been heavy kava users in the past but had abstained for longer than 6 months. Current and ex-kava users showed a higher rate of kava dermopathy, lower body mass index, lowered blood lymphocytes and, in addition, current kava users showed elevated liver enzymes. While there has recently been increasing concern about potentially fatal liver damage attributed to kava use, we have found no evidence of brain dysfunction in heavy and long-term kava users.

 

Management of chronic hepatitis B virus infection in remote-dwelling Aboriginals and Torres Strait Islanders: an update for primary healthcare providers.

Fisher DA, Huffam SE.

Royal Darwin Hospital, PO Box 41326, Casuarina, NT 0811, Australia. dale.fisher@nt.gov.au

Med J Aust 2003;178:82-5

Abstract: Chronic HBV infection is common in remote Aboriginal and Torres Strait Islander communities, where resources are scarce and patients may have several concurrent illnesses. The management of chronic HBV infection has changed over recent years, with greater application of serological and radiological investigations and new, more acceptable treatments for chronic liver disease, cirrhosis and hepatocellular carcinoma. Optimal follow-up procedures for patients with chronic HBV infection are still being debated, but may not be applicable to Aboriginal and Torres Strait Islander communities where factors such as endemicity, remoteness, frequent co-morbidities, shorter life expectancy and cultural differences in health priorities must be taken into consideration. We have defined an algorithm to assist primary care providers caring for patients with chronic HBV infection in Aboriginal and Torres Strait Islander communities. Patients are divided into one of three categories for follow-up and referral based on clinical features, and results of liver enzyme and serological tests.

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Generation and characterization of cDNA clones from Sarcoptes scabiei var. hominis for an expressed sequence tag library: identification of homologues of house dust mite allergens.

Fischer K, Holt DC, Harumal P, Currie BJ, Walton SF, Kemp DJ.

The Queensland Institute of Medical Research, The Australian Centre for International and Tropical Health and Nutrition, and The University of Queensland, Brisbane, Australia.

Am J Trop Med Hyg 2003;68:61-4

Abstract: Molecular studies on scabies, a disease of considerable human and veterinary significance, have been limited because of the difficulty of obtaining the causative organism Sarcoptes scabiei, the "itch mite." We have used skin from the bedding of crusted scabies patients as a source of mites for the construction of libraries of cDNAs from S. scabiei var. hominis in the bacteriophage lambda vector lambdaZAP express. Sequences of 145 clones established that the libraries predominantly contain sequences from S. scabiei, enabling a major sequencing program to begin. Among those sequenced to date, cDNAs encoding S. scabiei homologues of 3 house dust mite allergens-the M-177 apolipoprotein, glutathione S-transferase, and paramyosin--were identified. The availability of cDNA libraries from S. scabiei var. hominis and S. scabiei var. vulpes and the emerging public sequence databases from both opens up new possibilities in scabies research.

 

Identification of a homologue of a house dust mite allergen in a cDNA library from Sarcoptes scabiei var hominis and evaluation of its vaccine potential in a rabbit/S. scabiei var. canis model.

Harumal P, Morgan M, Walton SF, Holt DC, Rode J, Arlian LG, Currie BJ, Kemp DJ.

Menzies School of Health Research, Darwin, Northern Territory, Australia.

Am J Trop Med Hyg 2003;68:54-60

Abstract: Sarcoptes scabiei ("itch mite") causes scabies, a disease of considerable human and veterinary significance. Little work has been done at the molecular level because of the difficulty of obtaining mites. We have used mites in skin from the bedding of crusted scabies patients for the construction of a library of 10(5) cDNAs from S. scabiei var. hominis cloned in the vector pGEX4T-2. We describe the isolation by immunoscreening of 2 clones, one of which (Ssagl) is homologous to and cross-reactive with the house dust mite Euroglyphus maynei allergen M-177, an apolipoprotein from hemolymph. Immunohistochemistry revealed that it is located around the internal organs and cuticle of the mite and in eggs. Although it was not found to be protective in a challenge trial, the rabbits did not exhibit typical crust characteristics. This work shows that it is now possible to conduct such challenge trials with cloned scabies antigens.

 

Cystic Fibrosis and Burkholderia pseudomallei Infection: An Emerging Problem?

Holland DJ, Wesley A, Drinkovic D, Currie BJ.

LabPlus, Auckland Healthcare, Auckland, New Zealand.

Clin Infect Dis 2002;35:e138-40

Abstract: We recently managed 4 patients with cystic fibrosis who had acquired Burkholderia pseudomallei infection after exposure in a region of endemicity. Person-to-person transmission between 2 siblings may have occurred; otherwise, the evidence suggests that cystic fibrosis may increase the likelihood of infection with this organism, and patients should be warned of this possibility and cautioned to avoid high-risk activities.

 

Endemic invasive amoebiasis in northern Australia.

McCarthy JS, Peacock D, Trown KP, Bade P, Petri Jr WA, Currie BJ.

Australian Centre for International and Tropical Health and Nutrition, University of Queensland, Royal Brisbane Hospital, Herston, QLD, Australia.

Med J Aust 2002;177:570

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Factors supporting sustainability of a community-based scabies control program.

Wong LC, Amega B, Barker R, Connors C, Dulla ME, Ninnal A, Cumaiyi MM, Kolumboort L, Currie BJ.

Skin and Cancer Foundation, Sydney, New South Wales, Australia.

Australas J Dermatol 2002;43:274-7

Abstract: Scabies remains a major problem in Aboriginal communities within the Northern Territory of Australia. Secondary skin infection with Group A streptococcus (GAS) is very common and post-streptococcal disease rates remain high. Treating families in isolation will have only limited success, as reinfection frequently occurs as a result of the high levels of movement between households and communities. We describe the results of a successful community intervention to reduce scabies and GAS skin infection in one of the largest Aboriginal communities in the Northern Territory, 15 months post-intervention, and we discuss factors that have led to the success and sustainability of the program.

 

HIV-1 infection in foreign nationals working in East Timor.

Huffam S, Currie BJ, Knibbs P, Savage J, Krause V.

Lancet 2002;360:416

 

Evidence-based medicine and clinical practice.

Lowe M, Brewster D.

Northern Territory Clinical School & Royal Darwin Hospital.

J Paediatr Child Health 2003;39:145-146

 

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

Delvecchio A, Currie BJ, McArthur JD, Walker MJ, Sriprakash KS.

Menzies School of Health Research, Darwin, Australia.

Epidemiol Infect 2002;128:391-6

Abstract: 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 internalisation 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.

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Pulmonary manifestations of uncomplicated falciparum and vivax malaria: cough, small airways obstruction, impaired gas transfer, and increased pulmonary phagocytic activity.

Anstey NM, Jacups SP, Cain T, Pearson T, Ziesing PJ, Fisher DA, Currie BJ, Marks PJ, Maguire GP.

Tropical Medicine and International Health Unit, Menzies School of Health Research, Darwin.

J Infect Dis 2002;185:1326-34

Abstract: Despite recognition of acute respiratory distress syndrome in both falciparum and vivax malaria, disease-related changes in pulmonary function have not been defined, and underlying mechanisms are not well understood. Respiratory symptoms, pulmonary function, pulmonary phagocytic cell activity, and longitudinal changes were examined in 26 adults with uncomplicated falciparum, vivax, and ovale malaria after treatment. Self-limiting cough occurred in both falciparum (36%) and vivax or ovale (53%) malaria. In infection with each malaria species, admission measures of airflow and gas transfer were lower than predicted, and mean lung (99m)technetium-sulfur-colloid uptake was significantly increased. Changes were most evident in falciparum malaria, with treatment resulting in initial worsening of airflow obstruction and gas transfer. Altered pulmonary function in malaria is common and includes airflow obstruction, impaired ventilation, impaired gas transfer, and increased pulmonary phagocytic activity, and its occurrence in both vivax and falciparum malaria suggests that there may be common underlying inflammatory mechanisms.

 

Impact of single dose azithromycin on group A streptococci in the upper respiratory tract and skin of Aboriginal children.

Shelby-James TM, Leach AJ, Carapetis JR, Currie BJ, Mathews JD.

Menzies School of Health Research, Darwin, Australia.

Pediatr Infect Dis J 2002;21:375-80

Abstract: BACKGROUND: Aboriginal children living in remote Australia experience high rates of bacterial infection such as trachoma, otitis media and streptococcal skin infection, which often progress to associated chronic diseases in later life. METHODS: In February, 1995, single dose azithromycin was given to 130 Aboriginal children with trachoma and their contacts. The impact of this program on respiratory and skin group A Streptococcus pyogenes carriage and infection was also monitored. RESULTS: Immediately before treatment 90% of children had skin sores, 38% of sores had pus and 74% of sores with pus had group A Streptococcus (GAS). Overall 57% of children had GAS skin infections. At 2 to 3 weeks and 2 and 6 months after treatment, this proportion was 10, 32 and 51%, respectively. For the upper respiratory tract GAS recovery rates were 8% before treatment and 0, 11 and 15% at the 2- to 3-week, 2-month and 6-month post treatment visits, respectively. Multiple types occurred concurrently in individuals, particularly after treatment. Identical types were sometimes recovered simultaneously from the upper respiratory tract and skin, suggesting that the high rates of acute rheumatic fever in this population in the absence of high rates of detectable throat GAS carriage could be related to high rates of skin GAS infection. CONCLUSIONS: There is an urgent need for education, adequate housing, scabies eradication and improved hygiene to reduce skin trauma and subsequent GAS infection in this population. Clinical trials are needed to determine how these measures can best be integrated with the trachoma eradication program to maximize health outcomes.

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Community-acquired bacteremic Acinetobacter pneumonia in tropical Australia is caused by diverse strains of Acinetobacter baumannii, with carriage in the throat in at-risk groups.

Anstey NM, Currie BJ, Hassell M, Palmer D, Dwyer B, Seifert H.

Menzies School of Health Research, Royal Darwin Hospital, Northern Territory Clinical School, Darwin.

J Clin Microbiol 2002;40:685-6

Abstract: Acinetobacter isolates from eight subjects with community-acquired Acinetobacter pneumonia (CAAP), a major cause of fatal community-acquired pneumonia in tropical Australia, were phenotypically and genotypically confirmed by pulsed-field gel electrophoresis analysis to be broadly diverse Acinetobacter baumannii strains. Wet-season throat carriage of A. baumannii was found in 10% of community residents with excess levels of alcohol consumption, the major at-risk group for CAAP.

 

Paraplegia secondary to Burkholderia pseudomallei myelitis: a case report.

Haran MJ, Jenney AW, Keenan RJ, Flavell HD, Anstey NM, Currie BJ.

Department of Rehabilitation Medicine, Royal Darwin Hospital and Northern Territory Clinical School.

Arch Phys Med Rehabil 2001;82:1630-2

Abstract: 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 faecal 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.

 

Retrospective review of febrile neutropenia in the Royal Darwin Hospital, 1994-99.

Healey T, Selva-Nayagam S.

Intern Med J 2001;31:406-12

Abstract: BACKGROUND: Febrile neutropenia is a life-threatening complication of cytotoxic chemotherapy. Empirical antibiotic treatment should be based on predominant pathogens and epidemiological characteristics of the treated community. The aim of the present study was to review cases of febrile neutropenia at the Royal Darwin Hospital (RDH) in order to assess the appropriateness of empirical antibiotic therapy. METHODS: A retrospective review of cases of febrile neutropenia secondary to malignancy or chemotherapy occurring at the RDH over the period 1994-99. In order to compare infections in this group with those in the wider hospital community, all positive blood cultures in the medical and intensive care units were reviewed for the same time period. RESULTS: Thirty-six episodes of febrile neutropenia were reviewed. Staphylococcus aureus (predominantly methicillin resistant), Pseudomonas aeruginosa and Escherichia coli were the most common organisms identified. Nine patients died of their infection, four with methicillin-resistant S. aureus bacteraemia. S. aureus, E. coli, Streptococcus pneumoniae and Burkholderia pseudomallei (melioid) were the most frequently isolated organisms from blood cultures taken in the medical and intensive care units. CONCLUSIONS: Gram-positive organisms are the predominant pathogens in febrile neutropenic episodes at the RDH. Standard empirical therapy with an extended-spectrum penicillin and an aminoglycoside remains appropriate, with the addition of vancomycin when clinical status fails to improve. When practising in the Top End, particular consideration should be given to skin integrity and scabies and testing for Strongyloides in Aboriginal patients.

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

Jenney AW, Lum G, Fisher DA, Currie BJ.

Infectious Diseases Unit, Royal Darwin Hospital.

Int J Antimicrob Agents 2001;17:109-13

Abstract: 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.

 

Neurological melioidosis.

Currie BJ, Fisher DA, Howard DM, Burrow JN.

Division of Medicine, Royal Darwin Hospital, NT Clinical School and Menzies School of Health Research.

Acta Trop 2000;74:145-51

Abstract: 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.

 

Evaluation of a telemedicine link between Darwin and Adelaide to facilitate cancer management.

Olver IN, Selva-Nayagam S.

Telemed J 2000 6:213-8

Abstract: The videoconferencing link between the Royal Adelaide Hospital Cancer Centre in South Australia and the Royal Darwin Hospital in the Northern Territory was established to allow Darwin clinicians to discuss cases in multidisciplinary oncology meetings at the tertiary referral centre. This was evaluated by questionnaires distributed to the 20 health professionals involved and a group of 8 patients with breast cancer whose case histories had been discussed via videoconferencing. All clinicians found the telemedicine link to be either useful or very useful in at least one aspect of their practice. The major benefit was cited as enabling remote area clinicians to participate in multidisciplinary cancer meetings. Three of the 5 remote clinicians who practiced solely in the Northern Territory found that the telemedicine consultation increased their workload, while only 2 of 13 clinicians who practiced solely in South Australia reported an increase over their normal activities, the others reporting no difference. Benefits identified included better support of isolated clinicians, decreased travel, and enhanced education and peer review. Perceived difficulties were technical problems, the impersonal nature of the interaction, inability to examine the remote patient and lack of reimbursement for the consultation. Seven of the eight patients surveyed were satisfied or very satisfied with the telemedicine consultation. Four patients wished to have access to videotape of the multidisciplinary meeting. Of those requiring travel for treatment, all believed that the telemedicine consultation influenced their care and shortened their time away from home.

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Division of Surgery

 

A Unique Pattern of Urinary Tract Calculi in Australian Aboriginal Children

Carson PJ, Brewster DR

NT Clinical School & Royal Darwin Hospital

J Paediatr Child Health 2003 (in press)

Abstract: Young Aboriginal children in remote regions of tropical and desert Australia are at risk of developing urate stones in their upper urinary tract from an early age. These radiolucent calculi were only recognised with the availability of ultrasound diagnosis and are not associated with anatomic anomalies or abnormal uric acid production / metabolism. Although these stones appear to resolve spontaneously after the weaning period, some result in ureteric obstruction and infection which may lead to renal damage. This pattern of urolithiasis differs from the usual global urolithiasis pattern of either endemic bladder stones in young children in developing countries or predominantly calcium-based stones in upper tracts of older children and adults in affluent industrialised countries, where upper tract urate stones account for only a minority of childhood urinary tract stones. Risk factors for urate stones are low urine output and acidic urine. An association between urolithiasis and carbohydrate intolerance leading to chronic acidosis has been suggested for Aboriginal children, but existing limited evidence does not support this as a major aetiological factor. Although further studies on the epidemiology, natural history and management of these urate stones are needed, we believe the focus should be on improving the known social and environmental risk factors of remote Aboriginal children during the weaning period which contribute to the unacceptably high prevalence of failure to thrive, diarrhoeal disease, environmental enteropathy, iron deficiency and urolithiasis.

 

Flipped out of control: single-vehicle rollover accidents in the Northern Territory.

Treacy PJ, Jones K, Mansfield C.

Northern Territory Clinical School & Royal Darwin Hospital

Med J Aust 2002;176:260-3

Abstract: OBJECTIVES: To study the incidence of and factors associated with single-vehicle rollover (SVRO) accidents in the "Top End" of the Northern Territory (NT); to identify factors associated with major injury and death from SVRO accidents. DESIGN: Retrospective analysis of records from the NT Department of Transport and Works' police database, Royal Darwin Hospital's trauma database, coroner's records, and case notes from public hospitals in the Top End. STUDY POPULATION: All patients involved in SVRO accidents in the Top End between 1 January 1996 and 31 December 1997 whose accident was documented by the police, who attended a public hospital, or who died. MAIN OUTCOME MEASURES: Types and incidence of all accidents; details of the accident scene, vehicle features, and population groups associated with SVRO accidents; factors associated with major injury and death. RESULTS: SVROs accounted for 30% of all accidents and 29% of all injuries and deaths (441 people) in the whole of the NT over the study period. Some of the factors associated significantly more frequently with SVRO accidents were (i) occurrence of the accident on a straight, dry, unsealed road; (ii) presence of a vehicle defect; (iii) travelling at excessive speed; and (iv) the person being male, aged 41-50 years, of Aboriginal descent. Among the 147 people who were admitted to hospital or died from SVRO accidents in the Top End, major injury occurred significantly more frequently if the person was under the influence of alcohol, was not wearing a seatbelt and was ejected; if the accident occurred in a rural area; and if the vehicle was speeding. Major injuries occurred in 21% (31/147), and death was more likely in those with head, chest and neck injuries. CONCLUSION: SVRO accidents are a major cause of morbidity and mortality in the Top End of the NT. Effective methods of limiting speeding, drink-driving and driver fatigue should be sought. Populations most at risk should be targeted.

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Evaluation of amylase and lipase in the diagnosis of acute pancreatitis.

Treacy J, Williams A, Bais R, Willson K, Worthley C, Reece J, Bessell J, Thomas D.

Hepato-Biliary and Pancreatic Surgical Unit, Royal Adelaide Hospital, Flinders University of South Australia & Northern Territory Clinical School.

ANZ J Surg 2001;71:577-82

Abstract: BACKGROUND: The diagnosis of acute pancreatitis relies heavily on a raised amylase. METHODS: In the present study patients were prospectively categorized, without knowledge of pancreatic enzyme levels, into acute pancreatitis (AP; n = 51), disease controls (n = 35), indeterminate as to pancreatitis (n = 189) or exclusions (non-pancreatitis diseases where amylase may be elevated; n = 53). RESULTS: Enzyme levels were analysed by receiver operator characteristics (ROC) curves, with specificity > 80%. Day 1 serum lipase gave the greatest diagnostic accuracy (area under ROC curve = 0.128; P = 0.041 vs serum amylase). At the calculated diagnostic threshold of 208 U/L, lipase gave a sensitivity of 67% and a specificity of 97%. Other diagnostic thresholds (day 1) were: serum total amylase, 176 U/L (ROC 0.104, sensitivity 45%, specificity 97%), urinary total amylase, 550 U/L (ROC 0.108, sensitivity 62%, specificity 97%) and serum pancreatic isoamylase, 41 U/L (ROC 0.107, sensitivity 63%, specificity 85%). At delayed diagnosis (3 days) no enzyme was superior to lipase. The combination of lipase and amylase did not increase diagnostic accuracy. Conclusion: Serum lipase is recommended for diagnosis of AP, both early and late in the disease. Although highly specific when elevated, all pancreatic enzymes have low sensitivity for diagnosis.

 

Risks to feet in the Top End: outcomes of diabetic foot complications.

O'Rourke I, Heard S, Treacy J, Gruen R, Whitbread C.

Northern Territory Clinical School and Royal Darwin Hospital.

ANZ J Surg 2002;72:282-6

Abstract: BACKGROUND: The foot complications of diabetes are severe, disabling, costly and common in the Northern Territory. An understanding of the pathogenesis, the disease spectrum and treatment efficacy, however, is poor. The patterns of disease are documented in the present study; factors associated with good and poor outcomes are identified; and improved management strategies are proposed. METHODS: All patients presenting to the High Risk Foot Service at Royal Darwin Hospital between March 1997 and March 2000 were included in the present study, and details regarding the status of their feet, their demographics, their treatment and their outcomes were recorded prospectively. Logistic regression analysis was undertaken to determine associations between factors of interest and outcomes of healing and amputation. RESULTS: One hundred and twenty-six patients were recorded, 41% of whom had neuropathic ulcers and 63% of whom had severe disease at presentation. Two types of diabetic foot pathology were recognized that are not usually classified: acute injury without neuropathy (10%) and deep soft tissue infection alone (9%).Thirty-seven percent and 23% of patients required minor and major amputations, respectively. The total number of hospital bed-days was 5813. Total contact casting was associated with good healing rates in 16 patients. Major amputation was associated with ischaemia, severe disease at presentation and increasing age. CONCLUSIONS: Patterns of diabetic foot disease which are not commonly recognized are described in the present study; the severity and cost of the problem are documented; and some factors which lead to poor outcome, such as late presentation, are identified. Attention should be paid, through a multidisciplinary team, to timely referral from primary care, patient education, total contact casts and appropriate revascularization.

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Division of Critical Care

 

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

Stephens DP, Fisher DA, Currie BJ.

Royal Darwin Hospital, Tiwi, Northern Territory, Australia.

Intern Med J 2002;32:143-8

Abstract: 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 300µg 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.

 

 

Prospective study of jellyfish stings from tropical Australia, including the major box jellyfish Chironex fleckeri.

O'Reilly GM, Isbister GK, Lawrie PM, Treston GT, Currie BJ.

Royal Darwin Hospital.

Med J Aust 2001;175:652-5

Abstract: OBJECTIVE: To determine the immediate and delayed effects of jellyfish stings, and correlate these with microscopic identification of jellyfish nematocysts. DESIGN: Prospective study of patients presenting with jellyfish stings. Participants and setting: 40 people presenting with jellyfish stings to the emergency department of a teaching hospital in tropical Australia between 1 August 1999 and 31 July 2000. MAIN OUTCOME MEASURES: Clinical diagnosis (sting by Chironex fleckeri, "Darwin carybdeid" or other jellyfish, or "Irukandji" syndrome); clinical severity; delayed hypersensitivity; and sticky-tape sampling and microscopic identification of nematocysts. RESULTS: Patients were aged 2-50 years, with eight aged under 15 years; 23 were male. Presentations were consistent with C. fleckeri sting in 28 cases, Darwin carybdeid sting in five, and Irukandji syndrome in four. Sticky-tape sampling was done in 39 patients and was positive for C. fleckeri nematocysts in 23 and for non-C. fleckeri nematocysts in six, with nematocysts not detected in 10 (including all four with Irukandji syndrome). All microscopically confirmed C. fleckeri stings had typical clinical presentations. None of the stings were life-threatening, and no antivenom was given. Delayed hypersensitivity reactions were seen in 11 of the 19 patients (58%) followed up after stings positive for C. fleckeri nematocysts. CONCLUSIONS: Although most jellyfish stings presenting to Royal Darwin Hospital I were caused by C. fleckeri, severe envenomation was rare. There was a strong association between clinical features and sticky-tape identification of nematocysts. Delayed hypersensitivity was common after C. fleckeri stings.

 

Emergency department triage of indigenous and non-indigenous patients in tropical Australia.

Johnston-Leek M, Sprivulis P, Stella J, Palmer D.

Department of Emergency Medicine, Royal Darwin Hospital.

Emerg Med (Fremantle) 2001;13:333-7

Abstract: OBJECTIVE: To examine the relationship between ethnicity and triage at a tertiary hospital emergency department. METHODS: Electronic Emergency Department Information System data analysis was used to examine the relationship between ethnicity and triage allocation and process times between 1 April 1999 and 29 June 1999. Outcome measures were waiting times by triage category and admission rate by triage category. RESULTS: There were 9614 attendances: 1949 indigenous (20.3%), 7328 non-indigenous (76.2%) and 337 (3.5%) had no ethnicity recorded. Indigenous patients were more often female (1033; 53%, CI 51-55%) than non-indigenous patients (3078; 42.0%, CI 41-43%, P < 0.001). Indigenous patients presented more often with illness (70% CI 68-72%) rather than injury (30%, CI 28-32%), compared with the non-indigenous patients, illness (64%, CI 63-65%), injury (36%, CI 35-37%, P < 0.001). Indigenous patients were more likely to be triaged to national triage scale categories 1, 2 or 3 (36%, CI 34-38%) than non-indigenous patients (32%, CI 31-33%, P = 0.011). Admission rates for indigenous patients were higher than non-indigenous patients across all urgency categories and were within national triage scale guidelines. Non-indigenous admission rates were well below national triage scale guidelines for all urgency categories. The overall admission rate for indigenous patients was double (33%, CI 31-35%) that for non-indigenous patients (16%, CI 15-17%, P < 0.001). There was no significant difference between indigenous and non-indigenous waiting times. CONCLUSION: Indigenous patients are more likely to present with illness rather than injury and are more likely to require admission than non-indigenous patients. Indigenous patients are triaged in accordance with Australasian triage guidelines. Many non-indigenous patients should be triaged to lower urgency categories to allow resource allocation towards higher acuity indigenous and non-indigenous patients.

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

Isbister GK, Churchill TB, Hirst DB, Gray MR, Currie BJ.

Royal Darwin Hospital.

Med J Aust 2001;174:79-82

Abstract: 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.

 

Coagulopathy from tiger snake envenoming and its treatment.

Isbister GK, Currie BJ, Little M, Daly FF, Isbister JP.

Pathology 2002;34:588-90

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Department of Pathology

Clinical value of repeat Pap smear at the time of colposcopy.

Zardawi IM, Rode JW.

Mayne Health, Newcastle Laboratory, Newcastle, Australia.

Acta Cytol 2002;46:495-8

Abstract: OBJECTIVE: To determine the clinical value of a repeat (second) Pap smear at the time of colposcopy in the management of patients with recent cytologic abnormalities. STUDY DESIGN: A study of paired Pap smears and their corresponding cervical biopsies during a two-year period, commencing in June 1996, was undertaken. Pap smears and cervical biopsies from 614 patients were evaluated in the Department of Pathology, Royal Darwin Hospital, Northern Territory, Australia. To maintain uniformity, the cytologic and histologic findings were assessed according to the Bethesda System. RESULTS: The original (first) Pap smears included 288 high grade and 326 low grade lesions. The second smears showed 200 high grade, 221 low grade, 167 normal and 26 unsatisfactory cases. Punch biopsies revealed 242 high grade, 300 low grade and 72 inflammatory/reactive lesions. The changes noted in the second Pap smears and in the punch biopsies in the group originally diagnosed as having high grade disease were generally less advanced. The second Pap smears and corresponding cervical punch biopsies showed more advanced changes in the group originally diagnosed as having low grade disease. Removal of part of the abnormal epithelium during the first Pap smear and the desire of the colposcopist not to damage the surface epithelium prior to performing a cervical biopsy may account for some of these findings. Sampling errors and morphological misinterpretation may explain some of the findings. CONCLUSION: In the second smears, new cases of high grade abnormality were discovered mainly in patients with low grade changes on the first smears. Therefore, a second Pap smear at the time of colposcopy is justifiable in the group with low grade changes on the first smear.

 

Studies of measles viruses circulating in Australia between 1999 and 2001 reveals a new genotype.

Chibo D, Riddell M, Catton M, Lyon M, Lum G, Birch C.

Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia

Virus Res 2003;91:213-21

Abstract: Nineteen distinct measles virus (MV) strains associated with nine different genotypes were identified in five Australian states (Victoria, New South Wales, Queensland, Northern Territory and Western Australia) between 1999 and 2001. One of the strains identified is likely to represent a new genotype within the clade D viruses (proposed to be d9). No evidence for an indigenous MV strain was found. When epidemiologic information associated with the index case was available for the outbreaks, it usually supported introduction of the virus from overseas, with the main source being South East Asia. Changes in the circulation of MV in Australia since the early 1970s were also observed. Prior to the introduction of measles vaccine, the majority of the population acquired immunity through infection with wild-type virus in early childhood. Nowadays in Australia, young adults are at most risk of infection. The age range of cases in the study period was from 1 month to 48 years, with the majority (59%) of cases from individuals aged 18-30 years.

 

Does cleansing the birth canal at delivery reduce postnatal infection rates?

Murray RJ, Arthur AD, Delvecchio A, Finn M, Lum G, Currie BJ.

Royal Darwin Hospital

Med J Aust 2001;175:501-2

 

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Surveillance of antibiotic resistance in invasive isolates of Neisseria meningitidis in Australia 1994-1999.

Tapsall JW, Shultz T, Limnios E, Munro R, Mercer J, Porritt R, Griffith J, Hogg G, Lum G, Lawrence A, Hansman D, Collignon P, Southwell P, Ott K, Gardam M, Richardson CJ, Bates J, Murphy D, Smith H; National Neisseria Network of Australia.

Pathology 2001;33:359-61

Abstract: A total of 1434 strains of Neisseria meningitidis isolated from cases of invasive meningococcal disease (IMD) in Australia between 1994 and 1999 were examined by standard methods for susceptibility to antibiotics used for treatment and prophylaxis. The proportion of isolates fully susceptible to penicillin decreased from 45% in 1994 to 26% in 1999 (P<0.001). All the other isolates were less sensitive to penicillin except for two meningococci with a penicillin MIC of 1 mg/l. The geometric mean penicillin MIC increased from 0.045 to 0.065 mg/l from 1994 to 1999. There was no significant difference in the geometric mean penicillin MICs of serogroup B and serogroup C meningococci. Penicillin susceptibility was significantly associated with a poorer outcome. Isolates from survivors of IMD had a higher geometric mean penicillin MIC (0.06 mg/l) than those from fatal cases (0.048 mg/l) (P< 0.001). This suggests that factors other than the decrease in susceptibility to penicillin observed were more relevant to outcome in IMD. All isolates were fully susceptible to ceftriaxone. Rifampicin resistance was infrequent (eight isolates in 6 years) and sporadic. A single isolate had decreased quinolone susceptibility. Despite the significant shift in susceptibility to penicillin recorded, this group of antibiotics remains a suitable treatment for IMD in Australia.

 

 

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

Jenney AW, Lum G, Fisher DA, Currie BJ.

Infectious Diseases Unit, Royal Darwin Hospital, Darwin, NT 0810, Australia.

Int J Antimicrob Agents 2001;17:109-13

Abstract: 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.

 

 

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

Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, Selva-Nayagam S, Anstey NM, Huffam SE, Snelling PL, Marks PJ, Stephens DP, Lum GD, Jacups SP, Krause VL.

Division of Medicine and Pathology Department, Royal Darwin Hospital.

Clin Infect Dis 2000;31:981-6

Abstract: 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.

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