Hyperoxaluria, hyperglycoluria and renal oxalosis in Gilbert's potoroos (Potorous gilbertii).

CASE REPORT: Six Gilbert's potoroos (Potorous gilbertii) in a captive colony, five of which were closely related, died or were euthanased with severe renal disease. Clinical signs were mostly non-specific. Renal calculi were seen on ultrasound of two affected potoroos and oxalate crystalluria was seen in two of three affected potoroos that had urine samples examined. Necropsies revealed extensive severe renal oxalosis in all affected potoroos. These findings and markedly increased concentrations of glycolate in the urine of the four affected potoroos for which it was measured, confirmed a disorder of oxalate metabolism and suggested a condition similar to primary hyperoxaluria type 1 in humans. Liver alanine : glyoxylate aminotransferase activity and intracellular location were assessed as normal in one affected potoroo, which is inconsistent with human primary hyperoxaluria type 1. Although a condition similar to human primary hyperoxaluria type 2 or 3 was not ruled out, other clinicopathological findings were not consistent with those seen in humans with these conditions. A lack of faecal oxalate-degrading activity was observed in two affected potoroos in which it was measured, whereas oxalate-degrading activity was variably present in healthy captive and wild potoroos. CONCLUSION: Although the pathogenesis of renal oxalosis in these cases was not clear, the biochemical findings of elevated urinary oxalate and glycolate excretion indicate an abnormality of oxalate metabolism. The familial pattern of disease suggests it could be an inherited condition.

The innate resistance of Trypanosoma copemani to human serum.

Trypanosoma copemani is known to be infective to a variety of Australian marsupials. Characterisation of this parasite revealed the presence of stercorarian-like life-cycle stages in culture, which are similar to T. rangeli and T. cruzi. The blood incubation infectivity test (BIIT) was adapted and used to determine if T. copemani, like T. cruzi and T. rangeli, has the potential to grow in the presence of human serum. To eliminate any effects of anticoagulants on the complement system and on human high density lipoprotein (HDL), only fresh whole human blood was used. Trypanosoma copemani was observed by microscopy in all human blood cultures from day 5 to day 19 post inoculation (PI). The mechanism for normal human serum (NHS) resistance in T. copemani is not known. The results of this study show that at least one native Australian trypanosome species may have the potential to be infective for humans.

Further characterisation of two Eimeria species (Eimeria quokka and Eimeria setonicis) in quokkas (Setonix brachyurus).

The identification and characterisation of novel Eimeria species has largely been based on sporulated oocyst and sporocyst morphology, the host species and the geographical range. Variation in the size and shape of Eimeria oocysts across their host range however, make the identification and characterisation of novel species using traditional methodologies alone problematic. The use of molecular markers and phylogenetic analysis has greatly advanced our ability to characterise Eimeria species and has recently been applied to understand evolutionary relationships among Eimeria species from Australian marsupials. In the present study, Eimeria species isolated from quokkas (Setonix brachyurus) captured from Two Peoples Bay, Bald Island and Rottnest Island, Western Australia, were morphologically identified as Eimeria quokka and Eimeria setonicis. Both Eimeria species were identified as being polymorphic in nature with regards to sporulated oocyst and sporocyst morphometrics. Phylogenetic analysis using 18S rRNA and COI (cytochrome c oxidase subunit 1) genes, grouped E. quokka and E. setonicis within the Eimeria marsupial clade together with Eimeria trichosuri from brushtail possums, Eimeria macropodis from tammar wallabies (Macropus eugenii) and several unidentified macropod Eimeria species from western grey kangaroos (Macropus fuliginosus). This study is the first to characterise E. quokka and E. setonicis by molecular analysis, enabling more extensive resolution of evolutionary relationships among marsupial-derived Eimeria species.

Vector of Trypanosoma copemani identified as Ixodes sp.

A total of 41 ticks were collected from 15 quokkas on Bald Island and 2 ticks from a Gilbert's potoroo from Two Peoples Bay. Three species of Ixodid ticks Ixodes australiensis, Ixodes hirsti and Ixodes myrmecobii were identified on the quokkas known to have a high prevalence of Trypanosoma copemani. Tick faeces from ticks isolated from 8 individual quokkas and a Gilbert's potoroo were examined with one identified as positive for trypanosomes. Faecal examination revealed trypanosomes similar to in vitro life-cycle stages of T. copemani. In total 12 ticks were dissected and trypanosomes found in sections of their midgut and haemolymph, 49 and 117 days after collection. Tick faeces, salivary glands and midguts from I. australiensis were screened using an 18S rRNA PCR with amplification seen only from the midguts. Sequencing showed 100% homology to T. copemani (genotype A) and 99.9% homology to the wombat (AII) isolate of T. copemani. Trypanosomes were only detected in I. australiensis as neither I. hirsti nor I. myrmecobii survived the initial 30-day storage conditions. We therefore identify a vector for T. copemani as I. australiensis and, given the detection of trypanosomes in the faeces, suggest that transmission is via the faecal-oral route.

Morphological and molecular characterization of Trypanosoma copemani n. sp. (Trypanosomatidae) isolated from Gilbert's potoroo ( Potorous gilbertii) and quokka ( Setonix brachyurus).

Little is known of the prevalence and life-cycle of trypanosomes in mammals native to Australia. Native Australian trypanosomes have previously been identified in marsupials in the eastern states of Australia, with one recent report in brush-tailed bettongs (Bettongia penicillata), or woylie in Western Australia in 2008. This study reports a novel Trypanosoma sp. identified in blood smears, from 7 critically endangered Gilbert's potoroos (Potorous gilbertii) and 3 quokkas (Setonix brachyurus) in Western Australia. Trypanosomes were successfully cultured in vitro and showed morphological characteristics similar to members of the subgenus Herpetosoma. Phylogenetic analysis of 18S rRNA gene sequences identified 2 different novel genotypes A and B that are closely related to trypanosomes previously isolated from a common wombat (Vombatus ursinus) in Victoria, Australia. The new species is proposed to be named Trypanosoma copemani n. sp.

Cutaneous papillomatosis and carcinomatosis in the Western barred bandicoot (Perameles bougainville).

A progressive wart-like syndrome in both captive and wild populations of the Western barred bandicoot (WBB) is hindering conservation efforts to prevent the extinction of this endangered marsupial. In this study, 42 WBBs exhibiting the papillomatosis and carcinomatosis syndrome were examined. The disease was characterized by multicentric proliferative lesions involving cutaneous and mucosal surfaces, which were seen clinically to increase in size with time. Grossly and histologically the smaller skin lesions resembled papillomas, whereas the larger lesions were most commonly observed to be squamous cell carcinomas. Large amphophilic intranuclear inclusion bodies were observed in hyperplastic conjunctival lesions of 8 WBBs under light microscopy. Conjunctival lesions from 2 WBBs examined using transmission electron microscopy contained a crystalline array of spherical electron-dense particles of 45-nm diameter, within the nucleus of conjunctival epithelial cells, consistent with a papillomavirus or polyomavirus. Conjunctival samples from 3 bandicoots that contained intranuclear inclusion bodies also demonstrated a positive immunohistochemical reaction after indirect immunohistochemistry for papillomavirus structural antigens. Ultrastructural and/or immunohistochemical evidence of an etiologic agent was not identified in the nonconjunctival lesions examined. Here we describe the gross, histopathologic, ultrastructural, and immunohistochemical findings of a papillomatosis and carcinomatosis syndrome recently identified in the WBB.

Klossiella quimrensis (Apicomplexa: Klossiellidae) causes renal coccidiosis in western barred bandicoots Perameles bougainville (Marsupialia: Peramelidae) in Western Australia.

Previous studies have described a range of Klossiella species parasitic in marsupial hosts. Klossiella quimrensis is the etiologic agent of renal coccidiosis in the peramelid marsupial hosts Isoodon obesulus and Perameles gunnii in Eastern Australia, but there is no previous report of klossiellosis in Western Australian peramelids. This study describes klossiellosis diagnosed by histology of renal tissue sections collected during necropsy of 20 Perameles bougainville between 2000 and 2005. Sporonts, sporoblasts, and macrogametes were identified within parasitophorous vacuoles of epithelial cells located near the renal corticomedullary junction. The prevalence of renal coccidiosis in P. bougainville diagnosed by renal histology is estimated at 30%. Only a single unsporulated sporocyst was detected by examination of cystocentesis-collected urine, indicating that microscopic evaluation of urine samples is an insensitive diagnostic test for detection of K. quimrensis in P. bougainville. This infection in P. bougainville is indirectly associated with mild multifocal interstitial lymphohistiocytic nephritis and is likely to be only minimally pathogenic in otherwise healthy individuals. Our study also extends the host and geographic range of K. quimrensis to include P. bougainville and Western Australia.

Cryptococcosis in Gilbert's and long-nosed potoroo.

Two cases of fatal cryptococcosis are described, one of Cryptococcus neoformans infection in a Gilbert's potoroo (Potorous gilbertii) and one of Cryptococcus gattii infection in a long-nosed potoroo (Potorous tridactylus). The diagnoses were confirmed by culture and specific immunohistochemistry, respectively. The long-nosed potoroo tested positive using the latex cryptococcal antigen test (LCAT), whereas the Gilbert's potoroo had a negative LCAT result despite having advanced disease of some duration. In both cases, the clinical presentation was a progressive neurologic disease associated with a central nervous system infection. Pulmonary infection was also observed in the long-nosed potoroo. Specific treatment with antifungal agents was unsuccessful in the long-nosed potoroo.

Cryptosporidium muris infection in bilbies (Macrotis lagotis).

Cryptosporidiosis is an enteric disease of animals and humans that can be fatal in immunocompromised individuals. There is no known effective treatment for cryptosporidiosis. Bilbies are threatened marsupials and are bred in captivity as part of a recovery program to re-introduce this species to the southwest of Western Australia. Cryptosporidium muris infection was detected in the faeces of bilbies at a captive breeding colony. Stress associated with a high density of bilbies in enclosures may have predisposed some of the bilbies to infection with C. muris. C. muris has been described in mice and was found in the faeces of one mouse trapped in the breeding enclosures. It is likely the bilbies acquired the infection from mice by faecal contamination of food and water. The infection cleared within 2 months from some bilbies, however others remained infected for 6 months and treatment was attempted with dimetridazole. Subsequently the parasite was no longer be detectable in the faeces.

A randomised trial of self-management planning for adult patients admitted to hospital with acute asthma.

BACKGROUND: There is still debate over the benefit of self-management programmes for adults with asthma. A brief self-management programme given during a hospital admission for acute asthma was tested to determine whether it would reduce readmission. METHOD: A randomised controlled trial was performed in 280 adult patients with acute asthma admitted over 29 months. Patients on the self-management programme (SMP) received 40-60 minutes of education supporting a written self-management plan. Control patients received standard care (SC). RESULTS: One month after discharge SMP patients were more likely than SC patients to report no daytime wheeze (OR 2.6, 95% CI 1.5 to 5.3), no night disturbance (OR 2.0, 95% CI 1.2 to 3.5), and no activity limitation (OR 1.5, 95% CI 0.9 to 2.7). Over 12 months 17% of SMP patients were re-admitted compared with 27% of SC patients (OR 0.5, 95% CI 0.3 to 1.0). Among first admission patients, OR readmission (SMP v SC) was 0.2 (95% CI 0.1 to 0.7), p<0.01. For patients with a previous admission, OR readmission was 0.8 (95% CI 0.4 to 1.6), p=0.6. SMP patients were more likely than SC patients to be prescribed inhaled steroids at discharge (99% v 92%, p=0.03), oral steroids (98% v 90%, p=0.06), and to have hospital follow up (98% v 84%, p<0.01) but adjustment for these differences did not diminish the effect of the self-management programme. CONCLUSIONS: A brief self-management programme during hospital admission reduced post discharge morbidity and readmission for adult asthma patients. The benefit of the programme may have been greater for patients admitted for the first time. The programme also had a small but significant effect on medical management at discharge.

Patient weighting of importance of asthma symptoms.

BACKGROUND: Quality of life measures are increasingly important in evaluating outcomes in asthma. If some asthma symptoms are more troublesome to patients than others, this may affect their contribution to outcome measures. This study was designed to assess the relative importance of common symptoms in adults with asthma. METHODS: A postal survey using conjoint analysis was performed in 272 adults attending hospital outpatient clinics with moderately severe asthma. Patients were asked to chose between "symptom scenarios" offering different combinations of levels of five common asthma symptoms over one week. Two versions of the questionnaire were used with identical scenarios presenting symptoms in different orders. Different patients answered the two versions. Regression analysis was used to calculate symptom weights for daytime cough, breathlessness, wheeze and chest tightness, and sleep disturbance. RESULTS: Symptom order, percentage predicted peak expiratory flow (PEF), and symptoms in the week before the survey did not influence the choice of scenario. In both questionnaires patients were more likely to choose scenarios with low levels of cough and breathlessness than low sleep disturbance, wheeze or chest tightness. Regression weights for cough (-0.52) and breathlessness (-0.49) were twice those of wheeze (-0.25), chest tightness (-0.27), and sleep disturbance (-0.25). For 12% of patients cough dominated patient preferences, regardless of all other symptoms. Age was inversely related to weight given by patients to breathlessness. CONCLUSIONS: The prominence of cough among other asthma symptoms was unexpected. Daytime cough and breathlessness had greater impact for patients than wheeze or sleep disturbance. Age influenced symptom burden, with younger patients giving greater weight to breathlessness than older patients. Conjoint analysis appears to be a useful method for establishing the relative importance of common symptoms.

Symptoms, quality of life, and health service contact among young adults with mild asthma.

This report assesses Quality of Life (QoL) and its relationship to current symptoms and prospective medical contact among 396 adult patients with asthma. Patients were 16 to 52 yr of age and in the care of family physicians in the northeast of Scotland. All patients had been prescribed asthma medication within the previous 3 mo. Mean %pred FEV(1) was 87.4, mean %pred PEF was 85.1; 41% reported respiratory symptoms every week in the month before interview. Patients completed the SF-36, SF-12, and St. George's Respiratory Questionnaire (SGRQ) scales. Although mean scores on the SF-36 and SF-12 were close to population norms for patients without chronic illness, the presence of any respiratory symptoms in the month before interview was related to significantly lower QoL scores on the SF-36 scales of Physical Functioning, Energy, Mental Health, Pain, and Health Perception: the SF-12 Physical Functioning scale, and the SGRQ Symptoms, Impact and Activities scales. Physician contact for asthma in the 12 mo after interview was significantly related to SF-36, SF-12, and SGRQ scores at time of interview; however, when adjusted for symptoms at time of interview, only the SGRQ scales remained significant predictors of prospective physician contact. We conclude that respiratory symptoms have significant impact on QoL among patients with mild asthma, measured by generic and respiratory QoL scales, but that a specific respiratory scale is better able to discriminate patients who will seek physician care for asthma.

Mitochondrial DNA sequence variation within the remnant populations of the endangered numbat (Marsupialia: Myrmecobiidae: Myrmecobius fasciatus).

The numbat has been reduced to two populations in Western Australia. To better understand the effects of range reduction on gene flow and genetic variation, and to address questions crucial for the species' management, we analysed mitochondrial DNA (mtDNA) sequences of free-ranging individuals and museum specimens. The results suggest recent connectivity between the remnant populations, although one of those may have lost significant amounts of genetic diversity during the recent population size reduction. We propose that for management purposes the remnant populations should be treated as a single historical lineage and that, subject to certain caveats, consideration should be given to population augmentation by translocation.

Requests for repeat medication prescriptions and frequency of acute episodes in asthma patients.

This study was conducted to determine if suboptimal use of inhaled steroid and over-reliance on bronchodilator medication to control asthma symptoms is associated with higher risk of acute asthma episodes. Details of repeat prescriptions for medication and use of health services over 12 months were collected for 754 adult outpatients with asthma; all were prescribed inhaled corticosteroid. Patients who requested less than five prescriptions per year were considered suboptimal users. Patients who requested seven or more bronchodilator prescriptions and less than five inhaled steroid prescriptions had significantly more family physician consultations for asthma episodes (p < 0.05), more hospital admissions (p < 0.05), and more disturbed nights in the week before hospital or family physician review (p < 0.05). Some patients with more severe asthma put themselves at risk by relying on bronchodilator medication rather than regular inhaled steroid for asthma control. Among patients who were low bronchodilator users, those who requested few inhaled steroid prescriptions were younger and more anxious but did not have an increased risk of acute asthma episodes.

Asthma, wheezy bronchitis, and atopy across two generations.

Although the prevalence of asthma has risen significantly during the last 30 yr, it is not clear whether this has occurred primarily in persons with a strong genetic predisposition to asthma and atopy or in other sections of the population. We have investigated outcomes in children of nuclear families selected through probands previously characterized by studies in 1964 and 1989 as having histories of persistent childhood onset atopic asthma, transient childhood wheezy bronchitis, and no respiratory symptoms or atopy. Children of wheezy bronchitic probands had a significantly better symptomatic outcome in adolescence, irrespective of the atopic status of the parent proband, than do children of either asthmatic or asymptomatic probands, suggesting that this may be a syndrome that shows familial aggregation and is distinct from asthma. Total serum IgE levels were significantly lower in children of nonatopic asymptomatic probands, including those with wheezing symptoms. In contrast children of nonatopic asymptomatic probands had an unexpectedly high prevalence of wheezing (33%), positive skin prick tests (56%), and positive specific serum IgE to common allergens (48%) that was similar to that found in children of atopic asthmatic probands. Our findings support the concept that wheezy bronchitis is a separate syndrome from atopic asthma. High total serum IgE levels within our population appear to be an important marker of genetic predisposition to atopy. Our data also suggest that much of the increase in asthma prevalence is associated with specific IgE sensitization and is occurring in persons previously considered to be at low risk of developing asthma or atopy.

Domiciliary nebuliser therapy--a valuable option in chronic asthma and chronic obstructive pulmonary disease?

Domiciliary nebulisers are in widespread use for patients who have severe chronic airways disease, both asthma and chronic obstructive pulmonary disease (COPD). We report a study of the use of domiciliary nebulisers designed to assess practical problems and the value of such therapy in preventing hospital admissions. A total of 405 patients underwent a structured interview at home and their case records were reviewed. Technical performance of the nebuliser compressors was assessed. The mean (SD) age of those interviewed was 64.5 (12) years. 185 patients had a physician diagnosis of asthma, and 208 had COPD. 87% patients used their nebuliser at least once daily. Side effects, reported by 54%, were related to frequency of use and commoner in younger patients. 29 subjects (7%) died within 2 years of receiving their nebuliser. Among the survivors, the 2 year periods before and after supply of the nebuliser were compared. The percentage of patients requiring hospital admission for exacerbations of lung disease fell from 56% to 46% (p < 0.01) but the number and duration of admissions was unchanged. Those whose admission duration increased had more severely impaired spirometry when the nebuliser was supplied and had lower activity scores and higher breathlessness scores at the time of interview indicating more severe disease. Approximately half of the compressors were malfunctioning and patients' understanding of the principles of nebuliser treatment was poor. The provision of domiciliary nebuliser can influence hospital admission in patients with obstructive airways disease. There is also a need for improved patient education and for technical support which may require the development of a nurse-run nebuliser service.

Risk factors for adult onset wheeze: a case control study.

Risk factors associated with adult onset wheeze were examined in a case control study of subjects aged 39-45 yr derived from a community cohort of 2,056 asymptomatic children originally studied in 1964. Participants included 102 cases with adult onset wheeze (since age 15) and 217 controls with no wheeze. Logistic regression analysis was used to determine independent risk factors for wheeze among all cases and three subgroups: doctor diagnosed asthma (n = 24), wheeze with chronic cough and phlegm (n = 31), and other wheeze (n = 47). The risk of adult onset wheeze among all cases increased with low socioeconomic status (relative risk [RR] 2.36), current smoking (RR 2.01), positive atopic status (RR 3.28), and positive family history of atopic disease (RR 5.49). Gender was not related to the risk of wheezing. The pattern of significant independent risk factors differed between the subgroups of cases. Socioeconomic status was associated with cough and phlegm and other wheeze. Smoking habit was only related to cough and phlegm. Atopy was associated with doctor diagnosed asthma and cough and phlegm. Family history of atopic disease was related to all subgroups, suggesting that despite apparent heterogeneity in diagnostic labeling, concurrent symptoms, and other risk factors, the different forms of adult onset wheeze may share a common allergic basis.

Quality of life and hospital re-admission in patients with chronic obstructive pulmonary disease.

BACKGROUND: There is some evidence that quality of life (QOL) in patients with chronic obstructive pulmonary disease (COPD) may predict clinical outcomes and use of resources. This study examined whether QOL scores could prospectively predict re-admission for COPD or death within 12 months of an original admission, and whether QOL scores predicted home nebuliser provision. METHODS: The study was carried out in all acute medical wards of Aberdeen Royal Infirmary, Woodend and City Hospitals, Aberdeen over 12 months. A total of 377 patients admitted with an exacerbation of COPD were identified in this time, 111 of whom were not included in the study because they refused the interview or died before discharge. The remaining 266 patients completed the St George's Respiratory Questionnaire (SGRQ). Information on spirometric parameters, nebuliser provision at discharge, provision of domiciliary oxygen, and re-admission within 12 months was collected from patient notes. RESULTS: The mean age of the patients was 68 years and 53% were men. The mean (SD) forced expiratory volume in one second (FEV1) was 38.8 (18.0)% predicted and forced vital capacity (FVC) was 58.9 (23.8)% predicted. Higher (worse) scores on the SGRQ were significantly related to re-admission for COPD in the next 12 months (difference = 4.8, 95% CI 1.6 to 8.0). Patients who were re-admitted and died from COPD did not differ in SGRQ scores from those who were re-admitted and survived for more than 12 months. Re-admission was not related to sex, age, or pulmonary function. One hundred and thirty eight patients did not have a home nebuliser before admission. Of these, 14 were provided with a home nebuliser at discharge. Patients provided with nebulisers had significantly worse SGRQ scores and worse FVC. The 41 patients given domiciliary oxygen did not differ in SGRQ or spirometric parameters. Logistic regression analysis of the three SGRQ subscales (Symptom, Impact and Activity), adjusting for lung function, age and sex, showed that all three subscales were significantly related to hospital readmission and that Impact scores were related to nebuliser provision. Women did not differ from men in Symptom scores on the SGRQ but differed markedly on the Activity and Impact scales. CONCLUSIONS: It is concluded that poor scores on the SGRQ, a QOL scale which measures patient distress and coping, are associated with re-admission for COPD and use of resources such as nebulisers, independent of physiological measures of disease severity.

Outcome of children of parents with atopic asthma and transient childhood wheezy bronchitis.

BACKGROUND: Childhood asthma and wheeze only in the presence of respiratory infection (wheezy bronchitis) appear to have different prognoses and may differ in their aetiology and heritability. In particular, slight reductions in lung function may be associated with episodes of wheezing associated with intercurrent viral infection. METHODS: Outcomes for wheezing symptoms and lung function were studied in 133 offspring of three distinct groups of 69 middle aged probands with childhood histories of (1) atopic asthma (n = 18), (2) wheeze associated with upper respiratory tract infection (wheezy bronchitis, n = 24), and (3) no symptoms (n = 27). Probands were selected from a previously studied cohort in which outcomes of wheezy bronchitis and asthma had been shown to differ. RESULTS: Children of probands with wheezy bronchitis had a lower prevalence of current wheezing symptoms. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in boys of probands with a history of wheezy bronchitis were significantly reduced compared with either of the other two groups (p < 0.0001). In a multivariate analysis, grouping based on parent proband had a significant effect on lung function, independent of factors such as symptoms, atopy or smoking history. CONCLUSIONS: The different symptomatic and lung function outcome in children of probands with wheezy bronchitis and asthma provides further evidence that wheezy bronchitis and asthma differ in their natural history and heritability, and suggests that there may be familial factors specific to each wheezing syndrome.