Outbreak of henipavirus infection, Philippines, 2014.

During 2014, henipavirus infection caused severe illness among humans and horses in southern Philippines; fatality rates among humans were high. Horse-to-human and human-to-human transmission occurred. The most likely source of horse infection was fruit bats. Ongoing surveillance is needed for rapid diagnosis, risk factor investigation, control measure implementation, and further virus characterization.

Continuing differences between health professions' attitudes: the saga of accomplishing systems-wide interprofessionalism.

OBJECTIVE: To compare four health professions' attitudes towards interprofessional collaboration (IPC) and their evaluations of a programme aimed at enhancing IPC across a health system. DESIGN: Questionnaire survey. SETTING: Australian Capital Territory health services. PARTICIPANTS: Sample of medical (38), nursing (198), allied health (152) and administrative (30) staff. INTERVENTION: s) A 4-year action research project to improve IPC. MAIN OUTCOME MEASURE: Questionnaire evaluating the project and responses to the 'Attitudes toward Health Care Teams' and 'Readiness for Interprofessional Learning' scales. RESULTS: Significant professional differences occurred in 90% of the evaluation items. Doctors were the least and administrative staff most likely to agree project aims had been met. Nurses made more favourable assessments than did allied health staff. Doctors made the most negative assessments and allied health staff the most neutral ratings. Improved interprofessional sharing of knowledge, teamwork and patient care were among the goals held to have been most achieved. Reduction in interprofessional rivalry and improved trust and communication were least achieved. Average assessment of individual goals being met was agree (31.9%), neutral (56.9%) and disagree (11.2%). On the two attitude scales, allied health professionals were most supportive of IPC, followed by nurses, administrators and doctors. CONCLUSIONS: Although overall attitudes towards IPC were favourable, only a third of participants reported that project goals had been achieved indicating the difficulties of implementing systems change. The response profiles of the professions differed. As in the previous research, doctors were least likely to hold favourable attitudes towards or endorse benefits from social or structural interventions in health care.

A four-year, systems-wide intervention promoting interprofessional collaboration.

BACKGROUND: A four-year action research study was conducted across the Australian Capital Territory health system to strengthen interprofessional collaboration (IPC) though multiple intervention activities. METHODS: We developed 272 substantial IPC intervention activities involving 2,407 face-to-face encounters with health system personnel. Staff attitudes toward IPC were surveyed yearly using Heinemann et al's Attitudes toward Health Care Teams and Parsell and Bligh's Readiness for Interprofessional Learning scales (RIPLS). At study's end staff assessed whether project goals were achieved. RESULTS: Of the improvement projects, 76 exhibited progress, and 57 made considerable gains in IPC. Educational workshops and feedback sessions were well received and stimulated interprofessional activities. Over time staff scores on Heinemann's Quality of Interprofessional Care subscale did not change significantly and scores on the Doctor Centrality subscale increased, contrary to predictions. Scores on the RIPLS subscales of Teamwork & Collaboration and Professional Identity did not alter. On average for the assessment items 33% of staff agreed that goals had been achieved, 10% disagreed, and 57% checked neutral. There was most agreement that the study had resulted in increased sharing of knowledge between professions and improved quality of patient care, and least agreement that between-professional rivalries had lessened and communication and trust between professions improved. CONCLUSIONS: Our longitudinal interventional study of IPC involving multiple activities supporting increased IPC achieved many project-specific goals. However, improvements in attitudes over time were not demonstrated and neutral assessments predominated, highlighting the difficulties faced by studies targeting change at the systems level and over extended periods.

Transmission of influenza on international flights, may 2009.

Understanding the dynamics of influenza transmission on international flights is necessary for prioritizing public health response to pandemic incursions. A retrospective cohort study to ascertain in-flight transmission of pandemic (H1N1) 2009 and influenza-like illness (ILI) was undertaken for 2 long-haul flights entering Australia during May 2009. Combined results, including survey responses from 319 (43%) of 738 passengers, showed that 13 (2%) had an ILI in flight and an ILI developed in 32 (5%) passengers during the first week post arrival. Passengers were at 3.6% increased risk of contracting pandemic (H1N1) 2009 if they sat in the same row as or within 2 rows of persons who were symptomatic preflight. A closer exposed zone (2 seats in front, 2 seats behind, and 2 seats either side) increased the risk for postflight disease to 7.7%. Efficiency of contact tracing without compromising the effectiveness of the public health intervention might be improved by limiting the exposed zone.

Mucosal immunization with the Moraxella Catarrhalis porin m35 induces enhanced bacterial clearance from the lung: a possible role for opsonophagocytosis.

Moraxella catarrhalis is a significant cause of respiratory tract infection against which a vaccine is sought. Several outer membrane proteins are currently under investigation as potential vaccine antigens, including the porin M35. We have previously shown that the third external loop of M35 was immunodominant over the remainder of the protein for antibody produced in mice against the refolded recombinant protein. However, as this loop is predicted to fold inside the porin channel we also predicted that it would not be accessible to these antibodies when M35 is expressed on the surface of the bacteria in its native conformation. This study investigated the functional activity of antibodies against M35 and those specific for the loop 3 region of M35 in vitro and in vivo. Antisera from mice immunized with M35 or the loop 3-deletion, M35loop3(-), recombinant proteins were not bactericidal but did have enhanced opsonic activity, whereas antibodies raised against the loop 3 peptide were not opsoniszing indicating that the immunodominant loop 3 of M35 was not accessible to antibody as we had previously predicted. Mucosal immunization with M35, M35 that had an antigenically altered loop 3 [M35(ID78)] and M35loop3(-) enhanced the clearance of M. catarrhalis from the lungs of mice challenged with live M. catarrhalis. The in vivo clearance of bacteria in the mice with the M35-derived protein constructs correlated significantly (p < 0.001) with the opsonic activity assessed an in vitro opsonophagocytosis assay. This study has demonstrated that the immunodominant B-cell epitope to loop 3 of the M. catarrhalis outer membrane protein M35 is not associated with immune protection and that M35-specific antibodies are not bactericidal but are opsoniszing. The opsoniszing activity correlated with in vivo clearance of the bacteria suggesting that opsoniszing antibody may be a good correlate of immune protection.

WITHDRAWN: Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis.

BACKGROUND: Acute bronchitis leading to ongoing exacerbations is a serious condition predisposed to by viruses, bacteria or environmental factors. It can be fatal. Antibiotic therapy is not particularly useful. An oral Haemophilus influenzae vaccine has been developed. OBJECTIVES: To assess the effects of an oral, monobacterial whole-cell, killed, nontypeable H. influenzae vaccine in protecting against recurrent acute episodes in chronic bronchitis. SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to January Week 4 2006), EMBASE (1990 to September 2005) and ISI Current Contents (2004 to May 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of the H. influenzae vaccine on patients with recurrent acute exacerbations of chronic bronchitis were included when there was overt matching of the vaccine and placebo groups on clinical grounds. DATA COLLECTION AND ANALYSIS: Three authors extracted data and assessed trial quality independently from original records and publications for incidence and severity of bronchitis episodes and carriage rate of nontypeable H. influenzae measured in the upper respiratory tract every three months following vaccination. MAIN RESULTS: Six trials were included in the study with a total of 440 participants. The vaccine reduced the incidence of bronchitic episodes at three months after vaccination (rate ratio is 0.69; 95% CI 0.41 to 1.14) and at six months after vaccination (rate ratio 0.82; 95% CI 0.62 to 1.09). If these results been statistically significant, they would have represented a reduction in acute bronchitic attacks for vaccinated individuals of 31% at three months, and 18% at six. The effect had disappeared by nine months. The severity of exacerbations in the treatment group, as measured by requirement to prescribe antibiotics, was likewise reduced by 58% at three months (Peto odds ratio = 0.42; 95% CI 0.16 to 1.13), and by 65% at six months (Peto odds ratio = 0.35; 95% CI 0.16 to 0.75). AUTHORS' CONCLUSIONS: Vaccinating patients with recurrent acute exacerbations of chronic bronchitis in the autumn may reduce the number and severity of exacerbations over the following winter. A large clinical trial is needed.

Radical sequestration by protein-bound 3,4-dihydroxyphenylalanine.

Protein-bound 3,4-dihydroxyphenylalanine (PB-DOPA), a redox-active product of protein oxidation, is capable of functioning as both a pro- and antioxidant. A number of in vitro and in vivo studies have demonstrated a toxic, non-toxic or even beneficial effect of free DOPA, however little investigation has examined the physiological activity of PB-DOPA. Being the major treatment available for Parkinson's disease, most studies have focused on the effect of DOPA within neurological cells or tissues, although the presence of PB-DOPA in other locations, for example within atherosclerotic plaques, suggests that broader research is needed to fully understand the physiological effects of both free and PB-DOPA. We hypothesise that the generation of PB-DOPA can trigger an enhancement of the cellular antioxidant defence system, thus enabling PB-DOPA to restrict and potentially terminate the initiating oxidative stress, minimising the level of oxidative damage. Using luminol-enhanced chemiluminescence, we demonstrate that free DOPA is capable of direct peroxyl radical scavenging, even in the presence of competing scavengers, and has a different effect to that of the parent amino acid, tyrosine. Furthermore, we show that both free and PB-DOPA, in combination or individually, were able to protect monocytes and macrophages from peroxyl radical-induced oxidative stress in vitro. These results confirm a role for both free and PB-DOPA in cellular antioxidant defences and suggest the possibility of using DOPA as a potential therapeutic for the treatment of diseases involving oxidative stress or the accumulation of oxidative damage.

Moraxella catarrhalis M35 is a general porin that is important for growth under nutrient-limiting conditions and in the nasopharynges of mice.

Moraxella catarrhalis is a gram-negative respiratory pathogen that is an important causative agent for otitis media and exacerbations of chronic obstructive pulmonary disease. We have previously predicted the outer membrane protein M35 to be a general porin, and in the current study, we have investigated the function of M35 and its importance for survival of M. catarrhalis in vivo. Lipid bilayer experiments reveal that refolded M35 functions as a channel that is typical of gram-negative bacterial porins. M35 forms wide and water-filled channels with a single-channel conductance of about 1.25 nS in 1 M KCl solution and has only a small selectivity for cations over anions. When the in vitro growth characteristics of two M35 deletion mutant strains of M. catarrhalis were compared to the wild-type parent isolates, the growth of the mutant strains was inhibited only under nutrient-poor conditions. This growth defect could be eliminated by additional glutamic acid, but not additional aspartic acid, glycine, sucrose, or glucose. The mutant strains compensated for the lack of M35 by enhancing their uptake of glutamic acid, and this enhanced rate of glutamic acid uptake was attributed to the compensatory upregulation of a protein of approximately 40 kDa. M35 was also found to be essential for nasal colonization of mice, demonstrating that its presence is essential for survival of M. catarrhalis in vivo. These results suggest that M35 is a general porin that is necessary for the uptake of important energy sources by M. catarrhalis and that it is likely that M35 is an essential functional protein for in vivo colonization.

An action research protocol to strengthen system-wide inter-professional learning and practice [LP0775514].

BACKGROUND: Inter-professional learning (IPL) and inter-professional practice (IPP) are thought to be critical determinants of effective care, improved quality and safety and enhanced provider morale, yet few empirical studies have demonstrated this. Whole-of-system research is even less prevalent. We aim to provide a four year, multi-method, multi-collaborator action research program of IPL and IPP in defined, bounded health and education systems located in the Australian Capital Territory (ACT). The project is funded by the Australian Research Council under its industry Linkage Program. METHODS/DESIGN: The program of research will examine in four inter-related, prospective studies, progress with IPL and IPP across tertiary education providers, professional education, regulatory and registration bodies, the ACT health system's streams of care activities and teams, units and wards of the provider facilities of the ACT health system. One key focus will be on push-pull mechanisms, ie, how the education sector creates student-enabled IPP and the health sector demands IPL-oriented practitioners. The studies will examine four research aims and meet 20 research project objectives in a comprehensive evaluation of ongoing progress with IPL and IPP. DISCUSSION: IPP and IPL are said to be cornerstones of health system reforms. We will measure progress across an entire health system and the clinical and professional education systems that feed into it. The value of multi-methods, partnership research and a bi-directional push-pull model of IPL and IPP will be tested. Widespread dissemination of results to practitioners, policymakers, managers and researchers will be a key project goal.

Optimization of oral immunization through receptor-mediated targeting of M cells.

Only a small number of oral vaccines are available for routine immunizations despite a significant research effort and a number of obvious advantages over parenteral vaccination. The major roadblock in the development of oral vaccines has been mostly attributed to a lack of ability to specifically target antigen to the mucosal immune system of the gastrointestinal tract. This commentary examines the accessing of M cells through receptor interaction on the apical surface of the cell in order to enhance the efficiency and efficacy of oral immunization. Three challenges have been identified (1) the availability of appropriate experimental models to study M cell targeting and transcytosis; (2) appropriate tools for investigating the specificity of targeting; and (3) the identification of priority targets on the apical surface of M cells.

Protein-bound 3,4-dihydroxy-phenylanine (DOPA), a redox-active product of protein oxidation, as a trigger for antioxidant defences.

Protein hydroperoxides and protein-bound 3,4-dihydroxy-phenylanine are amongst the major long-lived redox-active products during free radical attack on proteins. Protein-bound 3,4-dihydroxy-phenylanine can redox cycle between catechol and quinone form, and bind transition metals, whereas hydroperoxides are converted to stable hydroxides. The free amino acid 3,4-dihydroxy-phenylanine is a normal metabolite, an oxidation product of tyrosine, involved in pathways of dopamine and melanin production, and we have shown that it may be incorporated into protein-by-protein synthesis. However, physiological levels of protein-bound 3,4-dihydroxy-phenylanine are very low; yet remarkably elevated levels occur in some pathologies. We propose that, unlike free 3,4-dihydroxy-phenylanine, protein-bound 3,4-dihydroxy-phenylanine is a signal for the activation of cellular defences both against the oxidative fluxes during oxidative stress and against the oxidative damage which sometimes ensues. Unlike free 3,4-dihydroxy-phenylanine, the levels of protein-bound 3,4-dihydroxy-phenylanine can change 5-10-fold during oxidative damage in vivo, an appropriate property for a signalling molecule. We suggest mechanisms by which protein-bound 3,4-dihydroxy-phenylanine might trigger oxidative defences, via NF-kappaB and other transcription factors. Little evidence yet bears directly on this, but we discuss some implications of observations on free 3,4-dihydroxy-phenylanine supply to cells in vitro, to Parkinson's patients, and to animal models of the disease. Several of the effects of 3,4-dihydroxy-phenylanine in these situations may be mediated by the production and actions of protein-bound 3,4-dihydroxy-phenylanine. Some experimental tests of the hypothesis are outlined and some possible therapeutic implications.

Microbial pattern recognition receptors mediate M-cell uptake of a gram-negative bacterium.

The receptors involved in the sampling of particulate microbial antigens by the gut are largely unknown. Here we demonstrate for the first time in an in vitro M-cell model and in situ in isolated murine intestinal segments that the receptors TLR-4, PAF-R, and alpha5beta1 integrin are all involved in mediating bacterial uptake associated with transcytosis. The pattern of expression of TLR-4 and alpha5beta1 integrin differed between M cells and enterocytes. There was increased apical expression of TLR-4 in M-cell cultures, and it was present on the apical surface of murine M cells but not enterocytes in situ. In contrast, PAF-R was expressed equally by both cell types in vitro and was abundantly expressed throughout the intestinal epithelium. Inhibition of TLR-4 and PAF-R, but not TLR-2, reduced gram-negative bacterial uptake by both cell types, whereas inhibition of the apically expressed alpha5beta1 integrin significantly reduced the ability of M cells to translocate bacteria. Hence, the involvement of each receptor was dependent not only on differences in the level of receptor expression but the cellular localization. Using bacteria that had mutations that affected the bacterial lipooligosaccharide structure indicated that the oligosaccharide moiety was important in bacterial uptake. Taken together, the data suggest that pathogen-associated molecular pattern interactions with pattern recognition receptors are key factors in M-cell recognition of intestinal antigens for mucosal immune priming.

Characterization of a novel porin protein from Moraxella catarrhalis and identification of an immunodominant surface loop.

Moraxella catarrhalis is a gram-negative bacterium that is mainly responsible for respiratory tract infections. In this study we report a novel outer membrane protein (OMP), designated M35, with a molecular mass of 36.1 kDa. This protein was structurally homologous to classic gram-negative porins, such as OMP C from Escherichia coli and OMP K36 from Klebsiella pneumoniae, with a predicted structure of 8 surface loops and 16 antiparallel beta-sheets. The DNA sequences of the genes from 18 diverse clinical isolates showed that the gene was highly conserved (99.6 to 100% of nucleotides), with only one isolate (ID78LN266) having base variations that resulted in amino acid substitutions. Electrophoresis and analysis of recognition of the protein using mouse anti-M35 sera showed that M35 was expressed on the bacterial surface and constitutively expressed across M. catarrhalis isolates, with only ID78LN266 showing poor antibody recognition. Our results showed that the single amino acid mutation in loop 3 significantly affected antibody recognition, indicating that loop 3 appeared to contain an immunodominant B-cell epitope. The antibody specificity to loop 3 may be a potential mechanism for evasion of host immune responses targeted to M35, since loop 3 should theoretically orientate into the porin channel. Thus, M35 is a highly conserved, surface-expressed protein that is of significance for its potential functional role as an M. catarrhalis porin and is of interest as a vaccine candidate.

Mucosal immunization against respiratory bacterial pathogens.

Bacterial respiratory diseases remain a major cause of morbidity and mortality throughout the world. The young and the elderly are particularly susceptible to the pathogens that cause these diseases. Therapeutic approaches remain dependent upon antibiotics contributing to the persistent increases in antibiotic resistance. The main causes of respiratory disease discussed in this review are Mycobacterium tuberculosis, Corynebacterium diphtheriae, Bordatella pertussis, Streptococcus pneumoniae, non-typeable Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa. All these organisms initiate disease at the mucosal surface of the respiratory tract and thus the efficacy of the host's response to infection needs to be optimal at this site. Vaccines available for diseases caused by many of these pathogens have limitations in accessibility or efficacy, highlighting the need for improvements in approaches and products. The most significant challenges in both therapy and prevention of disease induced by bacteria in the respiratory tract remain the development of non-injectable vaccines and delivery systems/immunization regimens that improve mucosal immunity.