Seropositivity to Campylobacter and association with abortion and lamb mortality in maiden ewes from Western Australia, South Australia and Victoria.

This case-control study investigated associations between Campylobacter fetus or Campylobacter jejuni titre and reproductive outcomes in 22 flocks of Merino and non-Merino maiden ewes aged 1-2 years old. Campylobacter titres were also determined for multiparous ewes aged 3 years or older on the same farms. C. fetus 'positivity' (titre ≥1:80) was detected for 12% (57/462; 95% confidence interval [95% CI] 9.6 to 15.6) of maiden ewes and 31% (65/210; 95% CI 25.0 to 37.4) of mature ewes. The odds for failing to rear a lamb in C. fetus-'exposed' maiden ewes (titre ≥1:10) was 2.01 times that of seronegative ewes (95% CI 1.09 to 3.77; P = 0.027), but there was no association between C. fetus-'positivity' (titre ≥1:80) and failure to rise (OR 1.69; 95% CI 0.77 to 3.76; P = 0.191). C. fetus abortions were confirmed with microbial culture in one maiden ewe flock. In this flock, C. fetus titres fluctuated and often waned by lamb marking, highlighting the value of necropsies during abortion investigations. C. jejuni-'positivity' (titre ≥1:80) was detected for 44% (204/462; 95% CI 39.7 to 48.7) maiden ewes, but odds of failing to rear were decreased for C. jejuni-'positive' ewes (OR 0.52; 95% CI 0.32 to 0.83; P = 0.007). The association between Campylobacter serology and the reproductive outcome was inconsistent in these flocks. Serology should be considered in the context of other risk factors and used in conjunction with other strategies to investigate the impact of Campylobacter exposure on ewe reproductive performance such as monitoring for abortions and lamb necropsies to determine aetiological diagnosis, and vaccination trials.

Evolutionary dynamics of a cycad obligate pollination mutualism - Pattern and process in extant Macrozamia cycads and their specialist thrips pollinators.

Obligate pollination mutualisms are rare and few have been investigated deeply. This paper focuses on one such mutualism involving thrips in the genus Cycadothrips that pollinate cycads in the genus Macrozamia. Both represent old lineages relative to insects and plants generally, are endemic to Australia, and are mutually co-dependent. The phylogenetic analyses presented here demonstrate that the pollinator is much more diverse than previously considered, with each pollinator lineage being extremely specific to between one and three host species where these latter share part of their distribution. The new species diversity we demonstrate in Cycadothrips all presently falls under the species name C. chadwicki, and these different lineages diversified during two periods. An older divergence, beginning 7.3Mya (4.4-11.1, 95% HPD), resulted in three major lineages, and then further diversification within each of these three lineages took place at most 1.1Mya (0.6-1.8, 95% HPD). These divergence estimates correspond to times when aridification was increasing in Australia, suggesting that population fragmentation following climatic change has played a significant role in the evolutionary history of Cycadothrips and Macrozamia. This means that co-diversification of the host and pollinator in allopatry appears to be the dominant process affecting species diversity. Host switching is also clearly evident in the discrepancy between the divergence times of the C. chadwicki lineage and C. albrechti, about 10.8Mya (6.0-17.1, 95% HPD), and their hosts, at about 1.1Mya (0.2-3.4Mya, 95% HPD), in that the pollinator split pre-dates the origin of the associated host species of each. These results add to the body of evidence that the evolutionary processes important in obligate pollinator mutualisms are more varied than previously assumed.

Indications for diagnostic open biopsy of mammographic screen-detected lesions preoperatively diagnosed as fibroadenomas by needle biopsy and their outcomes.

AIM: To identify the clinical, radiological, and histopathological factors that resulted in a diagnostic open biopsy of mammographic screen-detected lesions diagnosed preoperatively as fibroadenomas by needle biopsy. MATERIALS AND METHODS: BreastScreen WA data over 10 year period from 1 January 1999 to 31 December 2008 was reviewed. RESULTS: Among the 760,027 women screened in Western Australia between 1999 and 2008, 31 had a fine-needle aspiration (FNA) or a core biopsy (CB) diagnosing a fibroadenoma and subsequently underwent a diagnostic open biopsy (DOB). Three were preoperatively diagnosed as fibroadenoma by initial FNA but subsequent CB showed that these were not fibroadenomas and, therefore, were excluded from the present series. Of the 28 cases, DOB identified 21 fibroadenomas, two cellular fibroadenomas, two benign phyllodes tumours, one malignant phyllodes tumour, one fibroadenoma containing ductal carcinoma in situ (DCIS), and one case of a 40mm adenosis tumour with a small 5mm fibroadenoma. The lesions ranged from 5-100mm in size with an average size of 28mm. DOB and CB results were concordant in 25 (89%) of the cases. The primary clinical indications for undergoing DOB included indeterminate histopathological findings of cellular fibroadenomas versus phyllodes tumour (n = 10), enlarging size (n = 4), large size (n = 5), fibroadenomas with atypia (n = 1), discordant radiological and pathological findings (n = 3), patient preference (n = 1), association with a second screen-detected lesion requiring excision (n = 2), and an unknown indication (n = 1). CONCLUSION: CB diagnosis of fibroadenomas is a safe diagnosis unless it has atypical clinical, radiological, or pathological features.

Managing the risk of iatrogenic transmission of Creutzfeldt-Jakob disease in the UK.

BACKGROUND: With the emergence of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (CJD) in the UK, there is concern about iatrogenic transmission, and the approach to managing this risk is unique. AIM: To describe and review CJD incident management and the notification of individuals 'at increased risk' as a strategy for reducing iatrogenic transmission. METHODS: A description of iatrogenic CJD transmission, the CJD Incidents Panel's role, the number and nature of CJD incidents reported and the individuals considered 'at increased risk' by mid-2012. FINDINGS: Seventy-seven UK cases of CJD are likely to have resulted from iatrogenic transmission, among recipients of human-derived growth hormone (64 cases), dura mater grafts (eight cases), blood transfusions (four cases) and plasma products (one case). To limit transmission, the Panel reviewed 490 incidents and advised on look-backs, recalls of blood and plasma products, and quarantining and disposing of surgical instruments. Additionally, on Panel advice, around 6000 asymptomatic individuals have been informed they are at increased risk of CJD and have been asked to follow public health precautions. CONCLUSION: The strategy to reduce iatrogenic transmission of CJD has been developed in a context of scientific uncertainty. The rarity of transmission events could indicate that incident-related exposures present negligible transmission risks, or--given the prolonged incubation and subclinical phenotypes of CJD--infections could be yet to occur or have been undetected. Scientific developments, including better estimates of infection prevalence, a screening test, or improvements in decontaminating surgical instruments, may change future risk management.

A tissue-specific enhancer of the prostate-specific membrane antigen gene, FOLH1.

Prostate-specific membrane antigen (PSMA) is an integral membrane protein that is highly expressed on the surface of prostate epithelial cells. It is also expressed on the vascular endothelium of a number of tumor types. We have used an enhancer trap approach with randomly cleaved overlapping DNA fragments from an approximately 55-kb P1 cosmid insert encompassing the 5' half and upstream sequences of the PSMA gene (FOLH1) to isolate an enhancer that strongly activates the FOLH1 core promoter region. The enhancer (PSME) is located in the third intron about 12 kb downstream from the start site of transcription and is characterized by a 72-bp direct repeat within a 331-bp core region. The PSME activates transcription from its own and heterologous promoters in prostate cell lines; enhancement is greatest in the PSMA-expressing cell line LNCaP (>250-fold). The PSME shows essentially no activity in five nonprostate cell lines. PSME-enhanced expression is repressed in the presence of androgen, mimicking the repression of the endogenous FOLH1 gene. The data demonstrate that both cell-type specificity and androgen regulation are intrinsic properties of the enhancer. These properties make the PSME an excellent candidate for regulation of gene expression in gene therapy approaches to prostate cancer.

The epidemiology of invasive pneumococcal disease in children in Far North Queensland.

OBJECTIVES: To describe the epidemiology of invasive pneumococcal disease in children under 5 years of age in Far North Queensland and to examine the potential impact of a seven- and 11-valent conjugate pneumococcal vaccine. METHODS: A review of all cases of invasive pneumococcal disease in children under 5 years of age in Far North Queensland over a 9 year period (1992-2000). The distribution of the serotypes of isolates causing invasive pneumococcal disease was compared with the serotypes contained in the two vaccines. RESULTS: The annual incidence in indigenous and non-indigenous children under 5 years of age was 163 (95% confidence interval (CI) 122-213) and 42 (95% CI 31-55) cases per 100 000 children, respectively. For children under 2 years of age, these figures were 297 (95% CI 208-411) and 71 (95% CI 49-100), respectively. There was a greater variety of serotypes isolated from indigenous children (n=17) than from non-indigenous children (n=9; P < 0.01). The serotypes within the seven-valent vaccine accounted for 62% (95% CI 46-75%) and 88% (95% CI 76-95%) of the isolates from indigenous and non-indigenous children, respectively (P < 0.01). Serotypes within the 11-valent vaccine accounted for 72% (95% CI 57-84%) of the isolates from indigenous children under 5 years of age, but did not account for any extra isolates from non-indigenous children. CONCLUSION: Although the seven- and 11-valent conjugate pneumococcal vaccines cover only approximately 60 and 70%, respectively, of the isolates that cause invasive disease in indigenous children in Far North Queensland, they nevertheless have the potential to prevent much morbidity in and hospitalization of these children. It will be essential to maintain surveillance following the introduction of conjugate pneumococcal vaccines so as to monitor changes in the incidence of invasive pneumococcal disease, particularly in high-risk children.

Recognising and responding to outbreaks of hepatitis A associated with child day-care centres.

OBJECTIVES: To assess the appropriateness of a protocol for recognising and responding to outbreaks of hepatitis A in child day-care centres and to determine if measles-mumps-rubella (MMR) vaccine was given too soon following the administration of normal human immunoglobulin (NIGH) to young children to control the outbreaks. DESIGN: Prospective surveillance to recognise cases of hepatitis A associated with, and outbreaks of hepatitis A in, day-care centres. MAIN OUTCOME MEASURES: The percentage of initial ('sentinel') cases of hepatitis A associated with day-care centres that were subsequently recognised as also being 'index' cases of outbreaks of hepatitis A in the centres, and the number of children 9-13 months of age when given NIGH who were subsequently given MMR less than three months later. RESULTS: Only 18 (16%) of the 114 sentinel day-care associated cases of hepatitis A were also index cases of outbreaks of hepatitis A in their respective centres. A total of 105 cases of hepatitis A were associated with the 18 outbreak centres; NIGH was administered to 928 (78%) of the attendee children, and to 105 (82%) of the susceptible staff, at the 18 centres. Three of the five children 9-13 months of age when given NIGH were given MMR less that three months later. CONCLUSIONS: Although outbreaks of hepatitis A were common events in day-care centres in north Queensland during the two-year study period, a single case of hepatitis A associated with a centre was a poor predictor of an outbreak within that centre. Precautions must be taken to ensure that live vaccines are not administered to young children too soon after NIGH.

The initial coverage and impact of the pneumococcal and influenza vaccination program for at-risk indigenous adults in Far North Queensland.

OBJECTIVES: To describe the initial coverage and impact of a pneumococcal and influenza vaccination program for at-risk Indigenous adults in Far North Queensland that formally commenced in 1996. DESIGN: Ascertainment of vaccine coverages, and prospective laboratory surveillance of invasive pneumococcal disease occurring in Indigenous adults in the region. MAIN OUTCOME MEASURES: Coverages of the first doses of both vaccines administered since 1995, and the incidence of invasive pneumococcal disease in Indigenous adults in the region between 1993-2000. RESULTS: Most (96% and 73%) of the Indigenous adults > or = 50 years of age received influenza and pneumococcal vaccines, respectively, for the first time between 1995-2000. Assuming that either 33% or 50% of Indigenous adults 15-49 years of age in Far North Queensland were eligible for vaccination, then either 109% or 72% of this population received influenza vaccine, and either 75% or 50% received pneumococcal vaccine, respectively, for the first time between 1995-2000. The incidence of vaccine-preventable invasive pneumococcal disease fell from 111 (95% confidence interval [CI] 77-154) cases per 100,000 per year in 1993/94 to 28 (95% CI 13-53) cases per 100,000 per year in 1999-2000 (p<0.05). CONCLUSION: Although there was a significant decline in the incidence of invasive pneumococcal disease, the vaccine coverages after five years of the program were suboptimal. Because of the difficulties in targeting the 15-49 years age group and because of unrecognised risk factors, we suggest that a universal Indigenous adult pneumococcal and influenza vaccination program should be considered.

The investigation of a 'cluster' of hepatitis B in teenagers from an indigenous community in North Queensland.

BACKGROUND: In early 1999, five teenagers from the same Indigenous community were notified as having hepatitis B. Hepatitis B vaccine should have been offered to this cohort of teenagers in a 'catch-up' program during the late 1980s when they were of pre-school age. OBJECTIVES: To determine the vaccination status of residents of the community born between 1981 and 1985 (inclusive) and to ascertain the prevalence of markers of hepatitis B infection and carriage in the incompletely vaccinated teenagers in this cohort. METHODS: Community health records were examined to identify all residents in the study cohort. Immunisation records were obtained from local hospital records and from a statewide computerised vaccination database. Serological tests for markers of hepatitis B infection and carriage were performed on blood samples from the incompletely vaccinated teenagers. RESULTS: Only 44% of 235 teenagers who had their vaccination status assessed were fully vaccinated. One hundred and eleven (47%) of the cohort had not received any hepatitis B vaccine. Over 90% of the incompletely vaccinated had been infected with the hepatitis B virus and 26% of these were hepatitis B carriers. CONCLUSIONS: Despite the availability of an effective hepatitis B vaccine and the recommendation for a catch-up program, the pre-school aged cohort of children at the community were not effectively targeted for vaccination. Hepatitis B remains a consequential infection in Indigenous communities in North Queensland. IMPLICATIONS: Initiatives to control hepatitis B need to be enhanced within existing maternal and child health, sexual health, alcohol and drug and chronic disease management programs.

Review of leptospirosis notifications in Queensland and Australia: January 1998-June 1999.

The World Health Organization/Food and Agricultural Organization Collaborating Centre for Reference and Research on Leptospirosis, Western Pacific Region, accredited since 1958, is part of Queensland Health Scientific Services, which provide tertiary level support in epidemiology, surveillance, training and diagnosis for hospitals and pathology laboratories across the State. Databases for leptospirosis on a global, Australian and State-wide basis are maintained on site and support public health authorities in Australia, WHO and the International Leptospirosis Society. Queensland data collated and analysed from leptospirosis questionnaires, and a brief overview of Australian data based on questionnaire responses for notified cases from 1998 to June 1999, are summarised. The increase in leptospirosis notifications (77%) during 1998 possibly signalled greater awareness of the disease by clinicians. There was a significant increase in leptospirosis notifications for children and students and a high rate of hospitalisation of cases. An outbreak in North Queensland during the first half of 1999 resulted in 184 notifications with over 50% of cases hospitalised. Polymorphic presentation of the disease with severe pulmonary haemorrhage is associated in particular with the serovar australis. Serovar zanoni continues to be a major cause of severe clinical leptospirosis. Several cases were diagnosed in tourists. One of these cases presented with severe respiratory distress and required 14 days in hospital.

Malaria and its implications for public health in Far North Queensland: a prospective study.

This prospective study's objectives were to describe the features of all episodes of malaria diagnosed in Far North Queensland (excluding the Torres Strait) and to assess how much of a threat they posed to the area's public health. Over a three-year period, 216 episodes of malaria were diagnosed (158 Plasmodium vivax and 68 P. falciparum infections). Most (82%) of the infections were acquired in Papua New Guinea (PNG). Approximately 70% of the episodes occurred in Australian citizens, about half of whom were in malaria-endemic countries for work; the remainder travelled abroad for recreation. Three-quarters of the Australian citizens with malaria had taken either no or inadequate prophylaxis. Australian citizens who had taken adequate prophylaxis were much less likely to develop P. falciparum than other types of malaria compared to those who took either no or inadequate prophylaxis (p = 0.01). Gametocytes were present in 121 (56%) of the episodes of malaria. Mosquito surveillance was carried out in response to 38 (31%) of these gametocytaemic episodes. Significant numbers of Anopheles farauti sensu lato mosquitoes were found close to the residence of a patient in 4 (11%) of these episodes. Only two occasions when local transmission could have possibly occurred were recognised. We do not believe malaria poses an important threat to the health of the public in Far North Queensland. Nevertheless, it remains an important problem for those who travel abroad to malarious areas.

Leptospirosis associated with severe pulmonary haemorrhage in Far North Queensland.

Pulmonary haemorrhage as a manifestation of leptospirosis is rarely diagnosed in developed countries. Five patients with proven leptospirosis associated with severe pulmonary haemorrhage presented to one hospital in Far North Queensland between January 1994 and June 1997. Four required admission to the intensive care unit and one patient died. Pulmonary haemorrhage is an uncommon but severe complication of leptospirosis and may be a source of diagnostic confusion in tropical areas of Australia.

Relative activity and specificity of promoters from prostate-expressed genes.

BACKGROUND: To evaluate their relative activity and specificity for prostate cells promoter and regulatory regions from three prostate-expressed genes-prostate-specific antigen (PSA), probasin, and relaxin H2-have been compared in prostate cell lines and in lines of breast, bladder, liver, kidney, lung, and ovarian origin. METHODS: After transfection into different cell types, the activity of promoters was assayed using linked reporter genes and normalized against that of the Rous sarcoma virus. Activity was measured both in the presence and in the absence of co-transfected androgen receptor (AR). RESULTS: PSA and probasin regulatory regions showed strong responsiveness to co-transfection of the AR in most cell types. The core PSA promoter region showed low activity and specificity, but the specificity and level of expression were substantially increased by inclusion of upstream sequences, particularly the enhancer region. Probasin promoter fragments showed specificity of expression for prostate cell lines but required AR for significant levels of expression. Relaxin promoter fragments directed significant AR-inducible expression in prostate cells but showed little specificity and variable AR responsiveness in other cell types. CONCLUSIONS: Of regulatory regions tested, a 430-base pair probasin promoter and PSA enhancer/core promoter showed the best combination of AR-stimulated prostate cell expression with limited expression in other cell types.

Characterisation and molecular typing of Burkholderia pseudomallei: are disease presentations of melioidosis clonally related?

Eighteen cases of culture positive melioidosis caused by Burkholderia pseudomallei, were seen in four geographically separate communities in North Queensland, Australia. The genetic inter-relatedness of the clinical isolates were compared utilising random amplification of polymorphic DNA (RAPD) and multilocus enzyme electrophoresis (MEE). The isolates segregated into two groups that correlated with clinical presentation rather than geographical location. This is the first described association between the varied clinical presentations of this condition and specific molecular type. If proven on larger studies, this may further our understanding of the pathogenesis of this important condition.

Pemphigus vulgaris in pregnancy with favourable foetal prognosis.

Pemphigus vulgaris is an immunobullous disease affecting the skin and mucous membranes most commonly during the fifth and sixth decades of life. Its occurrence in pregnancy is rare. We now report two severe cases of the disorder presenting during pregnancy and discuss its potential effects on the foetus and its management in pregnancy.

Pneumococcal vaccination: an important strategy to prevent pneumonia in Aboriginal and Torres Strait Island adults.

The objective of the study was to examine the appropriateness of the National Health and Medical Research Council (NHMRC) recommendations concerning pneumococcal vaccination for Aboriginal and Torres Strait Island adults. Laboratory surveillance of invasive pneumococcal disease identified 95 cases acquired by adults 15 years of age and over in Far North Queensland from 1992 to 1995. The most common diagnosis was pneumonia (77 per cent). Sixty-one cases (64 per cent) occurred in Aboriginal and Torres Strait Island adults, who acquired the disease at a younger age (mean 40 years) than did other adults (mean 50 years). Most (93 per cent) of the Aboriginal and Torres Strait Island adults had at least one of the pre-existing medical conditions in the NHMRC criteria for pneumococcal vaccination. The most common was 'alcohol abuse' (62 per cent). Fifty-three (93 per cent) of the pneumococcal isolates from the Aboriginal and Torres Strait Island adults who had pre-existing conditions were serotyped. Fifty (94 per cent) belonged to types included in the currently available pneumococcal vaccine. We conclude that the NHMRC recommendations for pneumococcal vaccination are appropriate, considering the pattern of invasive pneumococcal disease that occurs in Aboriginal and Torres Strait Island adults in Far North Queensland. Because pneumococcal vaccination can reduce the pneumonia-associated morbidity and premature mortality experienced by Aboriginal and Torres Strait Island adults, the vaccine should be offered routinely to those considered to be at risk, particularly young men who have recently begun to consume hazardous amounts of alcohol, and recently diagnosed diabetics.

Plasmodium vivax malaria acquired in far north Queensland.

In February 1996, vivax malaria was diagnosed in a man from a remote community in far north Queensland who had not visited a malarious area for the past 19 years. Microscopy and DNA studies of blood from other residents of the community did not identify a source of infection. It was suspected the infection was transmitted by mosquitoes from a neighbour who had been infected in Papua New Guinea, but whose blood was not available for DNA tests.

Nucleotide sequence of ovine adenovirus tripartite leader sequence and homologues of the IVa2, DNA polymerase and terminal proteins.

Ovine adenovirus OAV287 was previously isolated from sheep in Western Australia. Here we describe a portion of its genome between map units 10.3 and 31.7 which includes major ORFs for homologues of the IVa2 polypeptide and the DNA replication proteins, Terminal protein and DNA polymerase, as well as the N-terminal portion of the 52/55-kDa polypeptide. In addition, as a prelude to possible adaptation of this virus as a vector we have mapped the elements which make up the tripartite leader sequence of late mRNAs, thereby defining the probable location of the OAV major late promoter. In other human and animal adenovirus genomes, one or two VA RNA genes are encoded between the ORFs for Terminal protein and 52/55-kDa polypeptides. In OAV, these ORFs overlap, suggesting that if VA RNA genes are present, they may lie elsewhere in the OAV genome.

Unique genome arrangement of an ovine adenovirus: identification of new proteins and proteinase cleavage sites.

The completed sequence and genome organization of OAV287, a serologically distinct ovine adenovirus, is described. The genome of 29,544 bp has inverted terminal repeats that are only 46 bp in length. Many OAV genes are identified by their homology with other adenovirus (Ad) sequences but three groups of reading frames show little homology. One group at the left-hand end of the genome probably represents the E1A/E1B regions. Two others, on the complementary strand at the right-hand end of the genome, are tentatively proposed as the E4 and E3 regions. They are separated by approximately 1 kb of A/T-rich sequence of unknown function with E3 being adjacent to the terminus. Structural proteins V and IX of human Ads are absent from the OAV genome but a new, processed, 28-kDa virion polypeptide is encoded on the strand complementary to the proposed E1A region. The coding sequences for two other structural proteins are unidentified. The OAV penton protein lacks the region containing an Arg/Gly/Asp sequence that, in human adenoviruses, is thought to interact with cellular integrins to facilitate virus entry. Analysis of proteins and peptides in purified OAV identified several cleavage sites utilized by the Ad proteinase. Some of these were previously identified in human Ad proteins, but new sites, some of which did not conform to the known specificity of the human Ad proteinase, were also identified. The data emphasize that this ovine virus differs significantly from other known human and animal adenoviruses.

Integrons found in different locations have identical 5' ends but variable 3' ends.

The positions of the outer boundaries of the 5'- and 3'-conserved segment sequences of integrons found at several different locations have been determined. The position of the 5' end of the 5'-conserved segment is the same for six independently located integrons, In1 (R46), In2 (Tn21), In3 (R388), In4 (Tn1696), In5 (pSCH884), and In0 (pVS1). However, the extent of the 3'-conserved segment differs in each integron. The sequences of In2 and In0 diverge first from the conserved sequence, and their divergence point corresponds to the 3'-conserved segment endpoint defined previously (H.W. Stokes and R.M. Hall, Mol. Microbiol. 3:1669-1683, 1989), which now represents the endpoint of a 359-base deletion in In0 and In2. The sequence identity in In3, In1, In4, and In5 extends beyond this point, but each sequence diverges from the conserved sequence at a different point within a short region. Insertions of IS6100 were identified adjacent to the end of the conserved region in In1 and 123 bases beyond the divergence point of In4. These 123 bases are identical to the sequence found at the mer end of the 11.2-kb insertion in Tn21 but are inverted. In5 and In0 are bounded by the same 25-base inverted repeat that bounds the 11.2-kb insert in Tn21, and this insert now corresponds to In2. However, while In0, In2, and In5 have features characteristic of transposable elements, differences in the structures of these three integrons and the absence of evidence of mobility currently preclude the identification of all of the sequences associated with a functional transposon of this type.