Incidence, clinical spectrum, diagnostic features, treatment and predictors of paradoxical reactions during antibiotic treatment of Mycobacterium ulcerans infections

Background: Paradoxical reactions from antibiotic treatment of Mycobacterium ulcerans have recently been recognized. Data is lacking regarding their incidence, clinical and diagnostic features, treatment, outcomes and risk factors in an Australian population.

Methods: Data was collected prospectively on all confirmed cases of M. ulcerans infection managed at Barwon Health Services, Australia, from 1/1/1998-31/12/2011. Paradoxical reactions were defined on clinical and histological criteria and cases were determined by retrospectively reviewing the clinical history and histology of excised lesions. A Poisson regression model was used to examine associations with paradoxical reactions.

Results: Thirty-two of 156 (21%) patients developed paradoxical reactions a median 39 days (IQR 20-73 days) from antibiotic initiation. Forty-two paradoxical episodes occurred with 26 (81%) patients experiencing one and 6 (19%) multiple episodes. Thirty-two (76%) episodes occurred during antibiotic treatment and 10 (24%) episodes occurred a median 37 days after antibiotic treatment. The reaction site involved the original lesion (wound) in 23 (55%), was separate to but within 3 cm of the original lesion (local) in 11 (26%) and was more than 3 cm from the original lesion (distant) in 8 (19%) episodes. Mycobacterial cultures were negative in 33/33 (100%) paradoxical episodes. Post-February 2009 treatment involved more cases with no antibiotic modifications (12/15 compared with 11/27, OR 5.82, 95% CI 1.12-34.07, p = 0.02) and no further surgery (9/15 compared with 2/27, OR 18.75, 95% CI 2.62-172.73, p < 0.001). Six severe cases received prednisone with marked clinical improvement. On multivariable analysis, age ≥ 60 years (RR 2.84, 95% CI 1.12-7.17, p = 0.03), an oedematous lesion (RR 3.44, 95% CI 1.11-10.70, p=0.03) and use of amikacin in the initial antibiotic regimen (RR 6.33, 95% CI 2.09-19.18, p < 0.01) were associated with an increased incidence of paradoxical reactions.

Conclusions: Paradoxical reactions occur frequently during or after antibiotic treatment of M. ulcerans infections in an Australian population and may be increased in older adults, oedematous disease forms, and in those treated with amikacin. Recognition of paradoxical reactions led to changes in management with less surgery, fewer antibiotic modifications and use of prednisolone for severe reactions.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Background
Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.

Methods
The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.

Results
Only five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.

Conclusions
Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

A technique for examination of diagnostic characters of penicillate millipedes

We describe a simple method for examination of penicillate millipedes. The internal tissues are dissolved and the stain Fast Green used to give excellent contrast for dissection and to provide clear visualisation of characters necessary for identification of both freshly collected and museum specimens.

Graduate attributes as a focus for institution-wide curriculum renewal: innovations and challenges

Curtin University's Curriculum 2010 (C2010) initiative aimed at ensuring degree programs were excellent and sustainable. Before C2010, graduate attributes were not universally emphasised and indicators showed room for improvement in generic skills. C2010 focused on embedding graduate attributes through three strategies. The first was embedding graduate attributes in degree programs and mapping for constructive alignment of outcomes and assessments. The second strategy was related: programs were reviewed drawing on evidence including perspectives of graduates, employers and program teams on the relative importance of graduate attributes and the extent to which they were generally demonstrated or developed. The third strategy was a university-wide eportfolio system enabling students' self- and peer-assessment of graduate attributes. Since completion of C2010, proxy indicators show improvement. However, this paper highlights the challenges associated with graduate attributes and renewal. These include: academic staff engagement, the time needed for innovations to come to fruition and evidencing achievement of graduate attributes.

An interspecific Nicotiana Hybrid as a useful and cost-effective platform for production of animal vaccines

The use of transgenic plants to produce novel products has great biotechnological potential as the relatively inexpensive inputs of light, water, and nutrients are utilised in return for potentially valuable bioactive metabolites, diagnostic proteins and vaccines. Extensive research is ongoing in this area internationally with the aim of producing plant-made vaccines of importance for both animals and humans. Vaccine purification is generally regarded as being integral to the preparation of safe and effective vaccines for use in humans. However, the use of crude plant extracts for animal immunisation may enable plant-made vaccines to become a cost-effective and efficacious approach to safely immunise large numbers of farm animals against diseases such as avian influenza. Since the technology associated with genetic transformation and large-scale propagation is very well established in Nicotiana, the genus has attributes well-suited for the production of plant-made vaccines. However the presence of potentially toxic alkaloids in Nicotiana extracts impedes their use as crude vaccine preparations. In the current study we describe a Nicotiana tabacum and N. glauca hybrid that expresses the HA glycoprotein of influenza A in its leaves but does not synthesize alkaloids. We demonstrate that injection with crude leaf extracts from these interspecific hybrid plants is a safe and effective approach for immunising mice. Moreover, this antigen-producing alkaloid-free, transgenic interspecific hybrid is vigorous, with a high capacity for vegetative shoot regeneration after harvesting. These plants are easily propagated by vegetative cuttings and have the added benefit of not producing viable pollen, thus reducing potential problems associated with bio-containment. Hence, these Nicotiana hybrids provide an advantageous production platform for partially purified, plant-made vaccines which may be particularly well suited for use in veterinary immunization programs.

Patient engagement strategies used for hypertension and their influence on self-management attributes

Background. Several effective methods to facilitate patient self-management of hypertension are available in primary care. These include direct support from community pharmacists and general practice, and the use of home blood pressure (BP) monitoring. The aim of this study is to establish the prevalence of use of key strategies and to determine their independent relationship with patient self-management attributes.

Methods. A survey of patients with treated hypertension was undertaken in 27 community pharmacies. This established recent use of BP monitoring and advice from health professionals. Patient awareness of BP and targets, appropriateness of BP targets and adherence to anti-hypertensive medications were assessed as indicative self-management outcomes. Predictors of outcomes were determined using binary logistic regression.

Results. Overall, 215 surveys were returned. Two-thirds of patients were aged >65 years, and 45% had conditions warranting tighter BP control (<130/80 mmHg). Almost all patients reported monitoring of their BP in the previous year and 63% could report their most recent BP reading. Just 36% reported knowing a target BP, and 78% of reported targets were within guidelines recommendations. One-fifth (22%) monitored their own BP, and 15% reported non-adherence to medication. Doctors provided the large majority of professional advice. Self-monitoring or documentation of BP readings was independently associated with increased likelihood of BP and target BP being known.

Conclusions. Regular monitoring of BP does not automatically translate to professional advice. Increased uptake of patient self-monitoring should be promoted as a means of enabling self-management.

Factors associated with attributes of internal audit departments : a canonical analysis

This study explores internal audit (IA) practices in selected Ethiopian organizations to identify factors associated with attributes of IA departments. Analytical questionnaire survey responses of 188 IA directors and staff from Ethiopian government ministries, state-owned enterprises and private companies were used. Canonical analysis results show that IA proficiency, scope of IA work and quality of IA planning and execution are higher in organizations where organizational policy authorizing IA is clearly defined, organizational risk exposure is high and internal audit's linkage with external audit is strong. The findings suggest that in organizations that are exposed to high risk, management tends to appreciate IA's assistance in managing risk and thus strengthens IA. Results also suggest the importance of internal and external audit linkages and IA charter (or similar organizational policy) to strengthen IA. The study provides further evidence of differences in IA attributes between public and private sector entities.