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

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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

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.
