1: Genes Immun 2002 Nov;3(7):414-8
A promoter polymorphism in the gene encoding interleukin-12 p40 (IL12B) is associated with mortality from cerebral malaria and with reduced 0
Morahan G, Boutlis CS, Huang D, Pain A, Saunders JR, Hobbs MR, Granger DL, Weinberg JB, Peshu N, Mwaikambo ED, Marsh K, Roberts DJ, Anstey NM.
The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
Interleukin-12 (IL-12) is an important regulatory cytokine in infection and
immunity. Administration of IL-12 may reduce complications of severe malaria
in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit,
influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We therefore
investigated whether IL12B polymorphisms may affect the outcome of
severe malaria. Homozygosity for a polymorphism in the IL12B promoter was associated
with increased mortality in Tanzanian children having cerebral malaria but not
in Kenyan children with severe malaria. Furthermore, homozygotes for the IL12B
promotor polymorphism had decreased production of nitric oxide, which is in
part regulated by IL-12 activity. These studies suggest that IL12B
polymorphisms, via regulation of IL-12 production, may influence the outcome
of malaria infection in at least one African population.
doi:10.1038/sj.gene.6363909
PMID: 12424623 [PubMed - in process]
2: Pediatr Infect Dis J 2002 Aug;21(8):730-9
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.
BACKGROUND: Aboriginal children hospitalized 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 diarrheagenic 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 (28.9%), rotavirus
(26.5%), enteropathogenic (17.2%), spp. (10.7%), (7.2%) and (7.2%). High geometric
mean permeability ratios (95% confidence intervals) occurred with rotavirus
(19.6; 15.3 to 25.1), enteroaggregative (21.2; 15.3 to 29.3) and (23.0; 15.1
to 35.1) compared with 9.4 (6.8 to 13.1) for no pathogens. NO production was
highest for (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 ( <
0.001) for rotavirus with acidosis and osmotic diarrhea, for with wasting and
hypokalemia and for with severe and prolonged diarrhea.CONCLUSIONS: Cryptosporidium,
Strongyloides, rotavirus and enteroaggregative are important contributors to
the severe manifestations of acute gastroenteritis in Australian Aboriginal
children.
PMID: 12192160 [PubMed - indexed for MEDLINE]
3: Methods Mol Med 2002;72:469-74
Systemic nitric oxide production in human malaria. II. Analysis of mononuclear cell nitric oxide synthase type 2 antigen expression.
Saunders JR, Misukonis MA, Weinberg JB, Anstey NM.
Tropical Medicine and International Health Unit, Menzies School of Health Research, Darwin, Australia.
PMID: 12125143 [PubMed - in process]
4: Methods Mol Med 2002;72:461-7
Systemic nitric oxide production in human malaria. I. Analysis of NO metabolites in biological fluids.
Anstey NM, Boutlis CS, Saunders JR.
Tropical Medicine and International Health Unit, Menzies School of Health Research, Division of Medicine, Royal Darwin Hospital, Darwin, Australia.
PMID: 12125142 [PubMed - in process]
5: J Infect Dis 2002 May 1;185(9):1326-34
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, Northern Territory, Australia. anstey@menzies.edu.au
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.
PMID: 12001051 [PubMed - indexed for MEDLINE]
6: J Clin Microbiol 2002 Feb;40(2):685-6
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, Northern Territory, Australia. anstey@menzies.edu.au
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.
PMID: 11825997 [PubMed - indexed for MEDLINE]
7: Am J Trop Med Hyg 2001 Oct;65(4):309-17
Therapy of uncomplicated falciparum malaria: a randomized trial comparing artesunate plus sulfadoxine-pyrimethamine versus sulfadoxine-pyrimethamine alone in Irian Jaya, Indonesia.
Tjitra E, Suprianto S, Currie BJ, Morris PS, Saunders JR, Anstey NM.
National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia.
Combining artesunate with existing antimalarial drugs may improve cure rates,
delay emergence of resistance, and reduce transmission. We performed a randomized
comparative trial to quantify the effect of adding artesunate to sulfadoxine-pyrimethamine
in the treatment of uncomplicated falciparum malaria in Indonesia. Using a modified
1997 World Health Organization protocol for
assessment of therapeutic efficacy of antimalarial drugs, 105 patients (stratified
by age/ethnic group) were randomized: 53 received artesunate orally, 4 mg/kg
of body weight, a single daily dose for three days, plus sulfadoxine-pyrimethamine
orally (1.25 mg of pyrimethamine/kg of body weight), a single dose on day 0,
and 52 patients received sulfadoxine-pyrimethamine alone. Six from the combination
group were withdrawn from analysis, as were six of the sulfadoxine-pyrimethamine
group. Treatment failure rates on day 14 were 0% in the artesunate plus sulfadoxine-pyrimethamine
group and 8.7% in the sulfadoxine-pyrimethamine group (P = 0.12). Treatment
failure rates on day 28 were 4.4% and 15.2%, respectively (P = 0.16). Relative
risk of treatment failure at 28 days was 0.3 (95% confidence interval [CI] =
0.1-1.3). Mean fever clearance time (1.3 versus 1.7 days) and mean parasite
clearance time (1.4 versus 2.0 days) were both faster in the artesunate plus
sulfadoxine-pyrimethamine group than in the sulfadoxine-pyrimethamine group
(P = 0.08 and P < 0.0001, respectively). Only 20 (39.2%) of 51 patients treated
with artesunate plus sulfadoxine-pyrimethamine were still parasitemic on day
1 compared with 45 (86.5%) of 52 patients treated with sulfadoxine-pyrimethamine
alone (P = 0.000001, relative risk [RR] = 0.4, 95% CI = 0.3-0.6). Gametocyte
carriage was lower following artesunate plus sulfadoxine-pyrimethamine than
following sulfadoxine-pyrimethamine (RR = 0.5, 95% CI = 0.2-1.0 on day 7 and
RR = 0.5, 95% CI = 0.2-1.1 on day 14). Mild diarrhea, rash, and itching resolved
without treatment. Combined artesunate plus sulfadoxine-pyrimethamine resulted
in more rapid fever and parasiteclearance, was well tolerated, reduced risk
of treatment failure, and lowered gametocyte carriage.
Publication Types:
Clinical Trial
Randomized Controlled Trial
PMID: 11693875 [PubMed - indexed for MEDLINE]
8: Arch Phys Med Rehabil 2001 Nov;82(11):1630-2
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, Flinders University, Casuarina, Northern Territory, Australia.
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 fecal 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. Copyright 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation
PMID: 11689986 [PubMed - indexed for MEDLINE]
9: Br J Haematol 2001 Apr;113(1):255-7
Comment on:
Br J Haematol. 2000 Jun;109(4):891-4.
Will the high rates of post-treatment sexual stage parasitaemia seen in malaria-endemic areas make the optiMAL antigen test unreliable in predicting malaria treatment outcome?
Tjitra E, Anstey NM.
Publication Types:
Comment
Letter
PMID: 11328311 [PubMed - indexed for MEDLINE]
10: J Clin Microbiol 2001 Mar;39(3):1025-31
Persistent ICT malaria P.f/P.v panmalarial and HRP2 antigen reactivity after treatment of Plasmodium falciparum malaria is associated with gametocytemia and results in false-positive diagnoses of Plasmodium vivax in convalescence.
Tjitra E, Suprianto S, McBroom J, Currie BJ, Anstey NM.
Communicable Diseases Research Centre, National Institute of Health Research and Development, Jakarta, Indonesia.
A problem with rapid Plasmodium falciparum-specific antigen histidine-rich protein 2 (HRP2) detection tests for malaria is the persistence of antigen in blood after the disappearance of asexual-stage parasitemia and clinical symptoms, resulting in false-positive (FP) test results following treatment. The ICT P.f/P.v immunochromatographic test detects both HRP2 and a panmalarial antigen (PMA) found in both P. falciparum and Plasmodium vivax. To examine posttreatment antigen persistence with this test and whether persistent sexual-stage forms (gametocytes) are a cause of FP tests after treatment, we compared serial antigen test results with microscopy results from patients symptomatic with P. falciparum malaria in Indonesia for 28 days following treatment with chloroquine (CQ; n = 66), sulfadoxine-pyrimethamine (SP; n = 36), and artesunate plus sulfadoxine-pyrimethamine (ART + SP; n = 15). Persistent FP antigenemia following SP treatment occurred in 29% (HRP2) and 42% (PMA) of the patients on day 7 and in 10% (HRP2) and 23% (PMA) on day 14. The high rates of persistent HRP2 and PMA antigenemia following CQ and SP treatment were strongly associated with the presence of gametocytemia, with the proportion with gametocytes on day 7 posttreatment being significantly greater in those with FP results than in those with true-negative PMA and HRP2 results. Gametocyte frequency on day 14 post-SP treatment was also greater in those with FP PMA results. Following SP treatment, PMA persisted longer than HRP2, giving an FP diagnosis of P. vivax in up to 16% of patients on day 14, with all FP P. vivax diagnoses having gametocytemia. In contrast, PMA was rapidly cleared following ART + SP treatment in association with rapid clearance of gametocytemia. Gametocytes appear to be an important cause of persistent posttreatment panmalarial antigenemia in areas of endemicity and may also contribute in part to persistent HRP2 antigenemia following treatment.
PMID: 11230422 [PubMed - indexed for MEDLINE]
11: Trans R Soc Trop Med Hyg 2000 Sep-Oct;94(5):518
Erratum in:
Trans R Soc Trop Med Hyg 2001 Jan-Feb;95(1):80
Failure of the 'pan-malarial' antibody of the ICT Malaria P.f/P.v immunochromatographic test to detect symptomatic Plasmodium malariae infection.
Dyer ME, Tjitra E, Currie BJ, Anstey NM.
Tropical Medicine and International Health Unit, Menzies School of Health Research and Northern Territory Clinical School, Darwin, Northern Territory, Australia.
PMID: 11132380 [PubMed - indexed for MEDLINE]
12: Clin Infect Dis 2000 Oct;31(4):981-6
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, Northern Territory Clinical School, Flinders University, Casaurina, Northern Territory, Australia. bart@menzies.edu.au
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.
Publication Types:
Review
Review, Tutorial
PMID: 11049780 [PubMed - indexed for MEDLINE]
13: Trans R Soc Trop Med Hyg 2000 May-Jun;94(3):301-4
Melioidosis: acute and chronic disease, relapse and re-activation.
Currie BJ, Fisher DA, Anstey NM, Jacups SP.
Division of Medicine, Royal Darwin Hospital Clinical School, Flinders University, Northern Territory, Australia. bart@menzies.edu.au
In melioidosis-endemic regions the importance of re-activation of Burkholderia
pseudomallei from latent foci remains unclear. This topic was assessed in a
10-year prospective study (1989-99) of melioidosis in the tropical north of
the Northern Territory of Australia, together with other aspects of the nature
of melioidosis. Incubation period from defined inoculating events was previously
ascertained as 1-21 (mean 9) days. Of 252 total cases 244 (97%) were considered
to be from recent acquisition of B. pseudomallei infection and 8 (3%) were considered
to be re-activation from a latent focus. Acute illness occurred in 222 (88%)
cases; 30 (12%) cases had chronic illness (symptomatic for > 2 months). Of
the 207 patients surviving the initial illness, 27 (13%) had a confirmed relapse
(mean time from initial diagnosis of 8 months), with 5 relapsing twice. Of these
32 relapses, 15 (3 fatal) were associated with poor adherence to the eradication
therapy antibiotics and 10 (none fatal) were failures of eradication with doxycycline
monotherapy. Following initial intensive therapy with ceftazidime or meropenem
for at least 14 days, eradication therapy with trimethoprim-sulphamethoxazole
monotherapy for at least 3 months had been more successful.
PMID: 10975006 [PubMed - indexed for MEDLINE]
14: Acta Trop 2000 Feb 5;74(2-3):121-7
The epidemiology of melioidosis in Australia and Papua New Guinea.
Currie BJ, Fisher DA, Howard DM, Burrow JN, Selvanayagam S, Snelling PL, Anstey NM, Mayo MJ.
Division of Medicine, Royal Darwin Hospital Clinical School and Tropical Medicine and International Health Unit, Menzies School of Health Research, Casuarina, NT, Australia. bart@menzies.edu.au
Melioidosis was first described in Australia in an outbreak in sheep in 1949
in north Queensland (22 degrees S). Human melioidosis was first described from
Townsville (19 degrees S) in 1950. Melioidosis is hyperendemic in the Top End
of the Northern Territory (NT) and as in parts of northeastern Thailand it is
the commonest cause of fatal community-acquired septicemic pneumonia. In the
9 years since 1989 the prospective NT melioidosis study at Royal Darwin Hospital
(12 degrees S) has documented 206 culture confirmed cases of melioidosis, with
an average annual incidence of 16.5/100,000. Melioidosis is also seen in the
north
of Western Australia and north Queensland, including the Torres Strait Islands,
but is uncommon in adjacent Papua New Guinea. Serological studies suggest that
infection is rare in the Port Moresby region, but there is emerging evidence
of melioidosis from Western Province. The NT study has documented inoculating
events in 52 (25%) of cases, with an incubation period of 1-21 days (mean 9
days); 84% of cases had acute disease from presumed recent acquisition and 13%
had chronic disease (sick, > 2 months). In 4% there was evidence of possible
reactivation from a latent focus; 28 of 153 (18%) males had prostatic abscesses.
The overall mortality was 21% (43 cases), with a mortality rate in septicemic
cases (95) of 39% and in non-septicemic cases (103) of 4%. Pneumonia was the
commonest presentation in both groups and, in addition, eight patients (two
deaths) presented with melioidosis encephalomyelitis. Melioidosis clusters in
temperate Australia are attributed to animals imported from the north. Molecular
typing of Burkholderia pseudomallei isolates from temperate southwest Western
Australia showed clonality over 25 years. In this outbreak and in studies from
the NT, some soil isolates are molecularly identical to epidemiologically related
animal and human isolates. Molecular typing has implicated the water supply
in two clonal outbreaks in remote aboriginal communities in northern Australia.
Further prospective collaborative studies are required to evaluate whether there
are truly regional differences in clinical features of melioidosis
and to better understand how B. pseudomallei is acquired from the environment.
PMID: 10674639 [PubMed - indexed for MEDLINE]
15: J Infect Dis 1999 Dec;180(6):1994-2002
Erratum in:
J Infect Dis 2000 Jan;181(1):408
Nitric oxide synthase type 2 promoter polymorphisms, nitric oxide production, and disease severity in Tanzanian children with malaria.
Levesque MC, Hobbs MR, Anstey NM, Vaughn TN, Chancellor JA, Pole A, Perkins DJ, Misukonis MA, Chanock SJ, Granger DL, Weinberg JB.
Department of Medicine, VA and Duke University Medical Centers, Durham, North Carolina, USA.
Nitric oxide (NO) plays an important role in host resistance to infection with
a variety of organisms. Two recent reports from Gabon and Gambia identified
associations of malaria disease severity with the inducible NO synthase (NOS2)
promoter G-954C and short allele (<11 repeats) pentanucleotide microsatellite
polymorphisms, respectively. It was postulated that there would be a correlation
of these polymorphisms with malaria disease severity and with measures of NO
production in our cohort of Tanzanian children with malaria. In Tanzanian children,
15% were heterozygous or homozygous for the G-954C polymorphism, and 13% had
the short-allele microsatellite polymorphism. There was no significant correlation
of either polymorphism with disease severity or with measures of NO production
and NOS2 expression. Black and white Americans differed significantly in the
frequencies of these polymorphisms. The various association of these gene polymorphisms
with malaria severity in different populations underscores the complexity of
host resistance to malaria.
PMID: 10558957 [PubMed - indexed for MEDLINE]
16: Am J Trop Med Hyg 1999 Aug;61(2):253-8
Effects of age and parasitemia on nitric oxide production/leukocyte nitric oxide synthase type 2 expression in asymptomatic, malaria-exposed children.
Anstey NM, Weinberg JB, Wang Z, Mwaikambo ED, Duffy PE, Granger DL.
Tropical Medicine and International Health Unit, and Biostatistics Unit, Menzies School of Health Research, Darwin, Northern Territory, Australia.
Age appears to influence not only the acquisition of clinical immunity to malaria
but also the susceptibility to and clinical manifestations of severe malaria.
Asymptomatic malaria-exposed Tanzanian children have high production of nitric
oxide (NO) and universal expression of leukocyte NO synthase type 2 (NOS2),
which may protect against disease. To determine the effects of age and parasitemia
on NO production, we measured urine and plasma NO metabolites and leukocyte
NOS2 expression in 45 fasting, asymptomatic, malaria-exposed children of different
ages, stratifying parasitemia by thick film and polymerase chain reaction (PCR)
analysis. Although NO production was significantly higher in thick film-positive
children than in thick film-negative children, after
adjusting for age and gender, we were unable to detect a difference in NO production
in thick film-negative children between those who were PCR positive and PCR
negative. The relationship between age and NO production was determined using
a generalized additive model adjusted for the effects of gender and parasitemia.
Production of NO using all three measures was highest in infancy,
decreasing after the first year of life, and then increasing again after 5 years
of age. This pattern of age-related NO production is the reverse of the pattern
of age-related morbidity from cerebral malaria in coastal Tanzanian children.
Elevated production of NO in both infants and older children may be related
to age per se and malaria infection respectively, and may be one of the mediators
of the anti-disease immunity found most commonly in these two age groups.
PMID: 10463676 [PubMed - indexed for MEDLINE]
17: Am J Trop Med Hyg 1999 Aug;61(2):249-52
Nitric oxide, malaria, and anemia: inverse relationship between nitric oxide production and hemoglobin concentration in asymptomatic, malaria-exposed children.
Anstey NM, Granger DL, Hassanali MY, Mwaikambo ED, Duffy PE, Weinberg JB.
Tropical Medicine and International Health Unit, Menzies School of Health
Research, Darwin, Northern Territory, Australia.
The cause of the anemia associated with chronic, intermittent, asymptomatic.
Low-level parasitemia in children in malaria-endemic endemic areas is not well
understood. Nitric oxide (NO) decreases erythropoiesis, and it is likely an
important mediator of anemia of chronic disease. Production of NO is decreased
in acute uncomplicated and cerebral malaria, but it is increased in asymptomatic
Tanzanian children (with or without parasitemia). We hypothesized that chronic
overproduction of NO in these asymptomatic children contributes to the anemia
associated with subclinical/subpatent malaria. In 44 fasting, asymptomatic,
malaria-exposed, Tanzanian children, NO production (measured using fasting urine
NOx excretion) was inversely associated with hemoglobin concentration (P = 0.03,
controlling for age and gender). Using multiple linear regression, hemoglobin
concentration was negatively associated with parasitemia (P = 0.005). After
controlling for age and parasitemia, NO was no longer an independent predictor
of anemia. One of the mechanisms of parasite-related anemia in such children
may be through the adverse hematologic effects of parasite-induced NO production.
PMID: 10463675 [PubMed - indexed for MEDLINE]
18: J Clin Microbiol 1999 Aug;37(8):2412-7
Field evaluation of the ICT malaria P.f/P.v immunochromatographic test for detection of Plasmodium falciparum and Plasmodium vivax in patients with a presumptive clinical diagnosis of malaria in eastern Indonesia.
Tjitra E, Suprianto S, Dyer M, Currie BJ, Anstey NM.
Communicable Diseases Research Centre, National Institute of Health Research and Development, Jakarta, Indonesia.
In areas such as eastern Indonesia where both Plasmodium falciparum and Plasmodium
vivax occur, rapid antigen detection tests for malaria need to be able to detect
both species. We evaluated the new combined P. falciparum-P. vivax immunochromatographic
test (ICT Malaria P.f/P.v.) in Radamata Primary Health Centre, Sumba, Indonesia,
from February to May 1998 with 560 symptomatic
adults and children with a presumptive clinical diagnosis of malaria. Blinded
microscopy was used as the "gold standard," with all discordant and
20% of concordant results cross-checked blindly. Only 50% of those with a presumptive
clinical diagnosis of malaria were parasitemic. The ICT Malaria P.f/P.v immunochromatographic
test was sensitive (95. 5%) and specific (89.8%) for the
diagnosis of falciparum malaria, with a positive predictive value (PPV) and
a negative predictive value (NPV) of 88.1 and 96.2%, respectively. HRP2 and
panmalarial antigen line intensities were associated with parasitemia density
for both species. Although the specificity and NPV for the diagnosis of vivax
malaria were 94.8 and 98.2%, respectively, the overall sensitivity (75%) and
PPV
(50%) for the diagnosis of vivax malaria were less than the desirable levels.
The sensitivity for the diagnosis of P. vivax malaria was 96% with parasitemias
of >500/microl but only 29% with parasitemias of <500/microl. Nevertheless,
compared with the test with HRP2 alone, use of the combined antigen detection
test would reduce the rate of undertreatment from 14.7 to 3.6% for microscopy-positive
patients, and this would be at the expense of only a modest increase in the
rate of overtreatment of microscopy-negative patients from 7.1 to 15. 4%. Cost
remains a major obstacle to widespread use in areas of endemicity.
PMID: 10405377 [PubMed - indexed for MEDLINE]
19: Med J Aust 1999 Jan 4;170(1):48
Missing the diagnosis of donovanosis in northern Australia.
Mein JK, Anstey NM, Bowden FJ.
Publication Types:
Letter
PMID: 10026679 [PubMed - indexed for MEDLINE]
20: Methods Enzymol 1999;301:49-61
Measuring nitric oxide production in human clinical studies.
Granger DL, Anstey NM, Miller WC, Weinberg JB.
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City 84132, USA.
Publication Types:
Review
Review, Tutorial
PMID: 9919553 [PubMed - indexed for MEDLINE]
21: Am J Trop Med Hyg 1997 Aug;57(2):187-9
Seroepidemiology of Rickettsia typhi, spotted fever group rickettsiae,
and
Coxiella burnetti infection in pregnant women from urban Tanzania.
Anstey NM, Tissot Dupont H, Hahn CG, Mwaikambo ED, McDonald MI, Raoult D, Sexton
DJ.
Department of Paediatrics, Muhimbili Medical Centre, Dar es Salaam, Tanzania.
Immunofluorescent antibody (IFA) testing was performed on sera drawn from 150
pregnant women in the port city of Dar es Salaam, Tanzania. Prevalence of antibodies
to Rickettsia typhi was 28%, higher than in any of the 12 other African countries
in which serosurveys using IFA testing have been performed. Seroprevalence of
antibodies to spotted f ever group rickettsiae antigens was
25.3%, comparable with that found in other sub-Saharan countries endemic for
Amblyomma ticks. Only 4.7% of women were seropositive for Coxiella burnetii.
PMID: 9288814 [PubMed - indexed for MEDLINE]
22: Trans R Soc Trop Med Hyg 1997 Mar-Apr;91(2):238-40
Comment on:
Trans R Soc Trop Med Hyg. 1996 Jan-Feb;90(1):44-7.
Trans R Soc Trop Med Hyg. 1996 May-Jun;90(3):270-3.
Nitrate levels in malaria.
Anstey NM, Granger DL, Weinberg JB.
Publication Types:
Comment
Letter
PMID: 9196781 [PubMed - indexed for MEDLINE]
23: Hum Mutat 1997;10(1):58-64
An expanded histatin gene polymorphism and test of a possible disease resistant phenotype.
Araki M, Anstey NM, Mwaikambo ED, Dua A, Amberger E, Azen EA.
Department of Orthodontics, ASAHI University School of Dentistry, Gifu, Japan.
Histatins are small molecular weight salivary proteins that are important in the non-immune host defense system. Two frequent cis-linked coding-change mutations were previously described in exon 5 of the HIS2 gene of Blacks. The polymorphic mutant allele was termed HIS2(2) and the wild-type allele HIS2(1). We here describe two new non-coding change polymorphisms of the HIS2 gene: a deletion in intron 5 (7183-7198 del) and a C-->T mutation in exon 5 [C-->T (7104)] that characterize two new HIS2 alleles, HIS2(3) and HIS2(4) respectively. Both mutations occur on a HIS2(1) background. The HIS2(3) allele occurred only in Afro-Americans, but not in 67 Japanese, 51 Chinese and 50 Whites. Among 66 random DNA samples from Afro-Americans, frequencies of HIS2(1), HIS2(2), HIS2(3) and HIS2(4) were 0.67, 0.22, 0.05 and 0.07 respectively, with a heterozygosity of 0.45. The frequencies of the HIS2(4) allele in 50 Whites and 50 Chinese were 0.06, and 0.1 respectively. In a comparison of 60 matched saliva and DNA samples from the Afro-American population, the DNA-based mutation analysis reliably identified salivary histatin phenotypes. The salivary histatin polymorphism (inferred from PCR analysis) was used to test a biologically plausible hypothesis, that the mutant histatin phenotype (coded by the HIS2(2) allele) confers relative resistance to severe and fatal malaria. In a study of 185 Black Tanzanian subjects, there were no significant differences in HIS2(2) allelic frequencies between the various test groups: for 86 cerebral malaria subjects, 54 uncomplicated malaria subjects, and 45 combined asymptomatic parasitemia and health controls, HIS2(2) frequencies were 0.16, 0.17 and 0.17 respectively. Thus, there was no support for the hypothesis in this population.
PMID: 9222761 [PubMed - indexed for MEDLINE]
24: J Exp Med 1996 Aug 1;184(2):557-67
Nitric oxide in Tanzanian children with malaria: inverse relationship between malaria severity and nitric oxide production/nitric oxide synthase type 2 expression.
Anstey NM, Weinberg JB, Hassanali MY, Mwaikambo ED, Manyenga D, Misukonis MA,
Arnelle DR, Hollis D, McDonald MI, Granger DL.
Division of Infectious Diseases & International Health, Duke University
Medical
Center, Durham, North Carolina 27710, USA.
Nitric oxide (NO)-related activity has been shown to be protective against
Plasmodium falciparum in vitro. It has been hypothesized, however, that excess
NO production contributes to the pathogenesis of cerebral malaria. The purpose
of this study was to compare markers of NO production [urinary and plasma nitrate
+ nitrite (NOx)], leukocyte-inducible nitric oxide synthase type 2 (NOS2), and
plasma TNF-alpha and IL-10 levels with disease severity in 191 Tanzanian children
with and without malaria. Urine NOx excretion and plasma NOx levels (corrected
for renal impairment) were inversely related to disease severity, with levels
highest in subclinical infection and lowest in fatal cerebral malaria. Results
could not be explained by differences in dietary nitrate ingestion among the
groups. Plasma levels of IL-10, a cytokine known to suppress NO synthesis, increased
with disease severity. Leukocyte NOS2 antigen was detectable in all control
children tested and in all those with subclinical infection, but was undetectable
in all but one subject with cerebral malaria. This suppression of NO synthesis
in cerebral malaria may contribute to pathogenesis. In contrast, high fasting
NOx levels and leukocyte NOS2 in healthy controls and asymptomatic infection
suggest that increased NO synthesis might
protect against clinical disease. NO appears to have a protective rather than
pathological role in African children with malaria.
PMID: 8760809 [PubMed - indexed for MEDLINE]
25: Trans R Soc Trop Med Hyg 1996 Mar-Apr;90(2):147-51
Elevated levels of methaemoglobin in Tanzanian children with severe and uncomplicated malaria.
Anstey NM, Hassanali MY, Mlalasi J, Manyenga D, Mwaikambo ED.
Duke-Muhimbili Clinical Research Laboratory, Muhimbili Medical Centre, Dar es Salaam, Tanzania.
Elevated levels of methaemoglobin, the ferric form of haemoglobin incapable
of oxygen transport, have been previously found during Plasmodium vivax infections
and in acidotic infants. We measured methaemoglobin in the following 5 groups
of children with P. falciparum malaria admitted to Muhimbili Medical Centre,
Dar es Salaam, Tanzania. (i) Cerebral malaria (CM) with unrousable coma (n =
50), including 32 with complete recovery (CMCR) and 18 with death or neurological
sequelae (CMDS); (ii) malaria with severe anaemia but without severe respiratory
distress (SA; n = 6); (iii) uncomplicated malaria (UM; n = 37); (iv) asymptomatic
parasitaemia (AP; n = 5); and (v) healthy controls (HC; n = 34). Mean methaemoglobin
levels were elevated in all groups with malaria, forming up
to 16.4% of circulating haemoglobin. The degree of methaemoglobinaemia correlated
with disease severity and severity of anaemia. Mean methaemoglobin levels in
children with AP, UM, SA, CMCR and CMDS were 3.3%, 4.1%, 5.6%, 4.7% and 5.8%
respectively; the mean levels in those with clinical disease were significantly
higher than those in healthy controls (2.0%). Methaemoglobinaemia > 10% was
found in 5.4%, 16.7%, 12.5%, and 22.2% of those with UM, SA, CMCR and CMDS,
respectively. In the presence of parasite sequestration, impaired tissue perfusion,
and a reduction in oxygen carrying capacity of blood due to anaemia, a further
reduction in oxygen carrying capacity from even a modest concentration of methaemoglobin
is likely to exacerbate tissue hypoxia, perhaps critically so in a minority
of anaemic and acidotic patients with severe falciparum malaria.
PMID: 8761575 [PubMed - indexed for MEDLINE]
26: Aust N Z J Med 1995 Dec;25(6):736
Comment on:
Aust N Z J Med. 1995 Apr;25(2):182-3.
Systemic lupus erythematosus (SLE): different prevalences in different populations of Australian aborigines.
Anstey NM, Bastian I, Dunckley H, Currie BJ.
Publication Types:
Comment
Letter
PMID: 8770340 [PubMed - indexed for MEDLINE]
27: Postgrad Med J 1994 Oct;70(828):766
Comment on:
Postgrad Med J. 1993 Dec;69(818):934-7.
Community-acquired Acinetobacter pneumonia.
Currie B, Fisher D, Anstey N, Withnall K.
Publication Types:
Comment
Letter
PMID: 7880314 [PubMed - indexed for MEDLINE]
28: Aust N Z J Med 1993 Dec;23(6):646-51
Systemic lupus erythematosus in Australian aborigines: high prevalence, morbidity and mortality.
Anstey NM, Bastian I, Dunckley H, Currie BJ.
Medical Registrar, Royal Darwin Hospital, Casuarina, NT.
BACKGROUND: Racial differences occur in the incidence of systemic lupus erythematosus
(SLE). It has been suggested that SLE occurs at a higher prevalence and with
greater severity in Aboriginal Australians, but because of the small, widely
distributed population base, this has not been well documented. AIMS: To confirm
and document the clinical impression of an increased prevalence and severity
of systemic lupus erythematosus (SLE) in Aboriginal Australians, and to identify
prognostic indicators. METHODS: Top End Northern Territory (NT) Aborigines with
SLE on 1 January 1984 or diagnosed thereafter were followed until 1 January
1991. Epidemiological, clinical and serological data were collected. RESULTS:
Prevalence on 1 January 1991 estimated
at 1:1900, at least twice the estimated prevalence in non-Aboriginal Australians.
High frequencies of renal disease (62% with proteinuria > 0.5 g/day) and
autoantibodies to the Sm antigen (29%) were identified, contributing to the
high mortality. Five year survival rate was 60%, with 67% of deaths resulting
from infection. CONCLUSIONS: There is a high prevalence of SLE in NT
Aborigines. In view of probable under-recognition of mild cases the true prevalence
is likely to be even higher. Although morbidity and mortality may have been
overestimated for the same reason, both were found to be high. Improved living
conditions and health care delivery may improve prognosis.
PMID: 8141691 [PubMed - indexed for MEDLINE]
29: Lancet 1993 Apr 17;341(8851):1035
Comment on:
Lancet. 1993 Mar 13;341(8845):603-8
Lancet. 1993 Mar 13;341(8846):661-2.
Artemisinin compounds in treatment of malaria.
Anstey NM.
Publication Types:
Comment
Letter
PMID: 8096931 [PubMed - indexed for MEDLINE]
30: Clin Infect Dis 1992 Aug;15(2):374
Comment on:
Clin Infect Dis. 1992 Jan;14(1):56-65.
Use of cefotaxime for treatment of Acinetobacter infections.
Anstey NM.
Publication Types:
Comment
Letter
PMID: 1520774 [PubMed - indexed for MEDLINE]
31: Clin Infect Dis 1992 Jul;15(1):163-9
Neurological melioidosis: seven cases from the Northern Territory of Australia.
Woods ML 2nd, Currie BJ, Howard DM, Tierney A, Watson A, Anstey NM, Philpott J, Asche V, Withnall K.
Department of Medicine, University of Utah School of Medicine, Salt Lake City.
Pseudomonas pseudomallei, which causes melioidosis, is most commonly associated
with pulmonary infection. We describe seven patients who developed a neurological
syndrome as the predominant manifestation of melioidosis: this syndrome was
characterized by peripheral motor weakness (mimicking Guillain-Barre syndrome),
brain-stem encephalitis, aseptic meningitis, and respiratory failure. Neurological
melioidosis occurred in the absence of demonstrable foci of infection in the
central nervous system (CNS) in five of
six patients whose cerebrospinal fluid was available for culture. Computed tomography
and magnetic resonance imaging of the brain and spinal cord of these patients
were not suggestive of pyogenic infection, although the latter procedure detected
brain-stem encephalitis. Autopsy findings in one case confirmed brain-stem encephalitis
without evidence of direct bacterial infection. The clinical presentation of
neurological melioidosis includes features of an exotoxin-induced neurological
syndrome, with profound neurological disease occurring in the absence of apparent
direct infection of the CNS. This syndrome appears to be a newly recognized
clinical presentation of melioidosis.
PMID: 1617057 [PubMed - indexed for MEDLINE]
32: Aust N Z J Med 1992 Apr;22(2):169-70
Profound thrombocytopenia due to Plasmodium vivax malaria.
Anstey NM, Currie BJ, Dyer ME.
Publication Types:
Letter
PMID: 1530541 [PubMed - indexed for MEDLINE]
33: Proc Natl Acad Sci U S A 1992 Mar 15;89(6):2277-81
Extensive genetic diversity in the HLA class II region of Africans, with a focally predominant allele, DRB1*1304.
Hill AV, Allsopp CE, Kwiatkowski D, Taylor TE, Yates SN, Anstey NM, Wirima JJ, Brewster DR, McMichael AJ, Molyneux ME, et al.
Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom.
Molecular HLA class II typing of greater than 1700 individuals from The Gambia
in West Africa and Malawi in South-Central Africa revealed a striking diversity
of HLA DRB-DQB haplotypes as defined by restriction fragment length polymorphism
(RFLP); this diversity is twice as extensive as that found in northern Europeans.
Despite this diversity, sequence and PCR/oligonucleotide analysis
showed that the recently described variant DRB1*1304 is the commonest DRB1 allele
in The Gambia. The sequence, geographical distribution, and RFLP association
of this allele, together with homozygosity test results, suggest that DRB1*1304
may have arisen from DRB1*1102 and have reached its remarkably high frequency
as a result of recent directional selection. The prevalence of
this unusual allele has implications for trials of subunit vaccines in this
area. The extensive and distinctive HLA class II region polymorphism in sub-Saharan
Africans is consistent with evidence from other genetic loci implying an African
origin of modern Homo sapiens.
PMID: 1347946 [PubMed - indexed for MEDLINE]
34: Am J Hum Genet 1992 Feb;50(2):411-21
Interethnic genetic differentiation in Africa: HLA class I antigens in The Gambia.
Allsopp CE, Harding RM, Taylor C, Bunce M, Kwiatkowski D, Anstey N, Brewster D, McMichael AJ, Greenwood BM, Hill AV.
Molecular Immunology Group, University of Oxford, John Radcliffe Hospital, England.
A total of 752 individuals from The Gambia, west Africa who are representative
of the major ethnic groups in the capital, Banjul, were serologically typed
for HLA-A, -B, and -C antigens. Although all were typically "African"
in their antigenic profiles, some marked frequency differences were found between
the ethnic groups. Genetic distance comparisons with several other African
populations showed that, although these west African populations clustered closely
together, the positions of the various ethnic groups in The Gambia were consistent
with historical and linguistic evidence of their affinities with one another
and with other African populations. Despite the potential confounding effects
both of selection by infectious diseases and of genetic drift caused by local
differences in population structure, HLA frequencies appear to be of value in
measuring inter- and intraregional population affinities in sub-Saharan Africa.
PMID: 1734720 [PubMed - indexed for MEDLINE]
35: Clin Infect Dis 1992 Jan;14(1):83-91
Comment in:
Clin Infect Dis. 1993 Oct;17(4):820-1.
Community-acquired Acinetobacter pneumonia in the Northern Territory of Australia.
Anstey NM, Currie BJ, Withnall KM.
Department of Medicine, Royal Darwin Hospital, Casuarina, Australia.
Eleven cases of blood culture-positive, community-acquired pneumonia due to the human commensal Acinetobacter baumannii were studied in Darwin in the Northern Territory of Australia during the 10-year period from March 1981 through February 1991. Demographic risk factors included male gender, age of greater than 45 years, and Aboriginal ethnic background. Multiple clinical risk factors, including cigarette smoking, alcoholism, chronic obstructive airway disease, and diabetes mellitus, were noted in all cases and contributed to the high mortality (64%). In all cases pneumonia was clinically fulminant. A fatal outcome was strongly associated with inappropriate initial antibiotic therapy. All tested isolates of Acinetobacter were sensitive to gentamicin and resistant to cefotaxime. The 34 previously reported cases of community-acquired acinetobacter pneumonia are reviewed, and appropriate therapeutic regimens are identified.
PMID: 1571467 [PubMed - indexed for MEDLINE]
36: Southeast Asian J Trop Med Public Health 1991 Jun;22(2):281-3
Ross River virus disease presenting with hematuria.
Anstey N, Currie B, Tai KS.
Department of Medicine, Royal Darwin Hospital, Australia.
PMID: 1658950 [PubMed - indexed for MEDLINE]
37: Med J Aust 1991 Jan 7;154(1):71
Comment in:
Med J Aust. 1991 May 6;154(9):639-40.
Comment on:
Med J Aust. 1990 Oct 1;153(7):415-7.
Eosinophilic enteritis in the Northern Territory.
Currie B, Anstey N.
Publication Types:
Comment
Letter
PMID: 1984596 [PubMed - indexed for MEDLINE]