Clinical factors associated with the humoral immune response to influenza vaccination in chronic obstructive pulmonary disease

Background and objective Individuals with chronic obstructive pulmonary disease (COPD) are at a high risk of developing significant complications from infection with the influenza virus. It is therefore vital to ensure that prophylaxis with the influenza vaccine is effective in COPD. The aim of this study was to assess the immunogenicity of the 2010 trivalent influenza vaccine in persons with COPD compared to healthy subjects without lung disease, and to examine clinical factors associated with the serological response to the vaccine. Methods In this observational study, 34 subjects (20 COPD, 14 healthy) received the 2010 influenza vaccine. Antibody titers at baseline and 28 days post-vaccination were measured using the hemagglutination inhibition assay (HAI) assay. Primary endpoints included seroconversion (≥4-fold increase in antibody titers from baseline) and the fold increase in antibody titer after vaccination. Results Persons with COPD mounted a significantly lower humoral immune response to the influenza vaccine compared to healthy participants. Seroconversion occurred in 90% of healthy participants, but only in 43% of COPD patients (P=0.036). Increasing age and previous influenza vaccination were associated with lower antibody responses. Antibody titers did not vary significantly with cigarette smoking, presence of other comorbid diseases, or COPD severity. Conclusion The humoral immune response to the 2010 influenza vaccine was lower in persons with COPD compared to non-COPD controls. The antibody response also declined with increasing age and in those with a history of prior vaccination.

Evaluation of immune responses to influenza vaccination in chronic obstructive pulmonary disease

Background: Given that viral infections are common triggers for exacerbations of Chronic Obstructive Pulmonary Disease (COPD), current clinical guidelines recommend that all patients receive annual influenza vaccinations. A detailed examination of the immune response to vaccination in COPD has not previously been undertaken, so this study aimed to compare immune responses to influenza vaccination between COPD patients and healthy subjects. Methods: Twenty one COPD patients and fourteen healthy subjects were recruited and cellular immune function was assessed pre- and post- vaccination with trivalent inactivated influenza vaccine. Results: One month after vaccination, H1N1 specific antibody titres were significantly lower in COPD patients than in healthy controls (p=0.02). Multivariate analysis demonstrated that post vaccination antibody titres were independently associated with COPD, but not with age or smoking status. Innate immune responses to the vaccine preparation did not differ between the two populations. Serum concentrations of IL-21, a cytokine that is important for B cell development and antibody synthesis, were also lower in COPD patients than in healthy subjects (p<0.01). In vitro functional differences were also observed, with fewer proliferating B cells expressing CD27 (p=0.04) and reduced T-cell IFN-γ synthesis (p<0.01) in COPD patients, relative to healthy subjects. Conclusions: In conclusion, COPD was associated with altered immune responses to influenza vaccination compared to healthy controls with reductions in both T-cell and B-cell function. These findings provide a foundation for future research aimed at optimising the effectiveness of influenza vaccination in COPD.

Equine influenza in Australia

Letter to the editor.

Queensland pharmacist immunisation pilot phase 1 pharmacist vaccination - Influenza final report

The results of the pilot demonstrated that a pharmacist delivered vaccinations services is feasible in community pharmacy and is safe and effective. The accessibility of the pharmacist across the influenza season provided the opportunity for more people to be vaccinated, particularly those who had never received an influenza vaccine before. Patient satisfaction was extremely high with nearly all patients happy to recommend the service and to return again next year. Factors critical to the success of the service were: 1. Appropriate facilities 2. Competent pharmacists 3. Practice and decision support tools 4. In-­‐store implementation support We demonstrated in the pilot that vaccination recipients preferred a private consultation area. As the level of privacy afforded to the patients increased (private room vs. booth), so did the numbers of patients vaccinated. We would therefore recommend that the minimum standard of a private consultation room or closed-­‐in booth, with adequate space for multiple chairs and a work / consultation table be considered for provision of any vaccination services. The booth or consultation room should be used exclusively for delivering patient services and should not contain other general office equipment, nor be used as storage for stock. The pilot also demonstrated that a pharmacist-­‐specific training program produced competent and confident vaccinators and that this program can be used to retrofit the profession with these skills. As vaccination is within the scope of pharmacist practice as defined by the Pharmacy Board of Australia, there is potential for the universities to train their undergraduates with this skill and provide a pharmacist vaccination workforce in the near future. It is therefore essential to explore appropriate changes to the legislation to facilitate pharmacists’ practice in this area. Given the level of pharmacology and medicines knowledge of pharmacists, combined with their new competency of providing vaccinations through administering injections, it is reasonable to explore additional vaccines that pharmacists could administer in the community setting. At the time of writing, QPIP has already expanded into Phase 2, to explore pharmacists vaccinating for whooping cough and measles. Looking at the international experience of pharmacist delivered vaccination, we would recommend considering expansion to other vaccinations in the future including travel vaccinations, HPV and selected vaccinations to those under the age of 18 years. Overall the results of the QPIP implementation have demonstrated that an appropriately trained pharmacist can deliver safely and effectively influenza vaccinations to adult patients in the community. The QPIP showed the value that the accessibility of pharmacists brings to public health outcomes through improved access to vaccinations and the ability to increase immunisation rates in the general population. Over time with the expansion of pharmacist vaccination services this will help to achieve more effective herd immunity for some of the many diseases which currently have suboptimal immunisation rates.

Positive results in a real-time PCR for type A influenza associated with the use of an inactivated vaccine.

A real-time reverse transcription polymerase chain reaction (qRT-PCR) test for the matrix gene of type A influenza viruses was used during the 2007 Australian equine influenza (EI) outbreak in order to confirm diagnosis and, later, eradication of the virus. During the EI outbreak, horses being exported required vaccination and individual proof of freedom from EI. At the end of the outbreak, positive results were obtained from four horses destined for export, because of contamination of the samples with the vaccine. This report highlights the need for EI testing and vaccination to occur on separate days and with the collection of swabs for testing to precede vaccination.

The first five days: field and laboratory investigations during the early stages of the equine influenza outbreak in Australia, 2007.

Until August 2007, Australia was one of only three countries internationally recognised to be free of equine influenza (EI). This report documents the diagnosis of the first cases of EI in Australian horses and summarises the investigations that took place over the next 5 days. During that time, a multifocal outbreak was identified across eastern New South Wales and south-eastern Queensland. The use of an influenza type A pan-reactive real-time reverse transcription polymerase chain reaction allowed rapid confirmation of suspect cases of EI.

The August 2007 equine influenza response management framework.

This section outlines the most important issues addressed in the management of the response in the two infected states, New South Wales and Queensland. There were differences in the management of the response between the states for logistic, geographic and organisation structural reasons. Issues included the use of control centres, information centres, the problems associated with the lack of trained staff to undertake all the roles, legislative issues, controls of horse movements, the availability of resources for adequate surveillance, the challenges of communication between disparate groups and tracing the movements of both humans and horses.

High-level coordination and strategy in the 2007 equine influenza outbreak response.

The equine influenza (EI) outbreak presented many challenges that required high-level coordination and decision making, as well as the development of new approaches for satisfactory and consistent resolution. This paper outlines the elements of the national coordination arrangements, preparatory arrangements in place prior to the outbreak that facilitated national coordination, and some of the issues faced and resolved in the response.

Significant features of the epidemiology of equine influenza in Queensland, Australia, 2007.

An outbreak of equine influenza (EI) caused by influenza A H3N8 subtype virus occurred in the Australian states of Queensland and New South Wales in August 2007. Infection in the Australian horse population was associated with the introduction of infection by horses from overseas. The first case of EI in Queensland was detected on 25 August 2007 at an equestrian sporting event. Infection subsequently spread locally and to other clusters through horse movements prior to the implementation of an official standstill. There were five main clusters of infected properties during this outbreak and several outliers, which were investigated to find the potential mechanism of disease spread. To contain the outbreak, Queensland was divided into infection status zones, with different movement controls applied to each zone. Vaccination was implemented strategically in infected areas and within horse subpopulations. Control and eventual eradication of EI from Queensland was achieved through a combination of quarantine, biosecurity measures, movement control, rapid diagnostic testing and vaccination.

Risk-based surveillance for avian influenza control along poultry market chains in South China: The value of social network analysis.

Over the past two decades, the poultry sector in China went through a phase of tremendous growth as well as rapid intensification and concentration. Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 was first detected in 1996 in Guangdong province, South China and started spreading throughout Asia in early 2004. Since then, control of the disease in China has relied heavily on wide-scale preventive vaccination combined with movement control, quarantine and stamping out. This strategy has been successful in drastically reducing the number of outbreaks during the past 5 years. However, HPAIV H5N1 is still circulating and is regularly isolated in traditional live bird markets (LBMs) where viral infection can persist, which represent a public health hazard for people visiting them. The use of social network analysis in combination with epidemiological surveillance in South China has identified areas where the success of current strategies for HPAI control in the poultry production sector may benefit from better knowledge of poultry trading patterns and the LBM network configuration as well as their capacity for maintaining HPAIV H5N1 infection. We produced a set of LBM network maps and estimated the associated risk of HPAIV H5N1 within LBMs and along poultry market chains, providing new insights into how live poultry trade and infection are intertwined. More specifically, our study provides evidence that several biosecurity factors such as daily cage cleaning, daily cage disinfection or manure processing contribute to a reduction in HPAIV H5N1 presence in LBMs. Of significant importance is that the results of our study also show the association between social network indicators and the presence of HPAIV H5N1 in specific network configurations such as the one represented by the counties of origin of the birds traded in LBMs. This new information could be used to develop more targeted and effective control interventions.

Bayesian estimation of the dynamics of pandemic (H1N1) 2009 influenza transmission in Queensland: A space–time SIR-based model

Background A pandemic strain of influenza A spread rapidly around the world in 2009, now referred to as pandemic (H1N1) 2009. This study aimed to examine the spatiotemporal variation in the transmission rate of pandemic (H1N1) 2009 associated with changes in local socio-environmental conditions from May 7–December 31, 2009, at a postal area level in Queensland, Australia. Method We used the data on laboratory-confirmed H1N1 cases to examine the spatiotemporal dynamics of transmission using a flexible Bayesian, space–time, Susceptible-Infected-Recovered (SIR) modelling approach. The model incorporated parameters describing spatiotemporal variation in H1N1 infection and local socio-environmental factors. Results The weekly transmission rate of pandemic (H1N1) 2009 was negatively associated with the weekly area-mean maximum temperature at a lag of 1 week (LMXT) (posterior mean: −0.341; 95% credible interval (CI): −0.370–−0.311) and the socio-economic index for area (SEIFA) (posterior mean: −0.003; 95% CI: −0.004–−0.001), and was positively associated with the product of LMXT and the weekly area-mean vapour pressure at a lag of 1 week (LVAP) (posterior mean: 0.008; 95% CI: 0.007–0.009). There was substantial spatiotemporal variation in transmission rate of pandemic (H1N1) 2009 across Queensland over the epidemic period. High random effects of estimated transmission rates were apparent in remote areas and some postal areas with higher proportion of indigenous populations and smaller overall populations. Conclusions Local SEIFA and local atmospheric conditions were associated with the transmission rate of pandemic (H1N1) 2009. The more populated regions displayed consistent and synchronized epidemics with low average transmission rates. The less populated regions had high average transmission rates with more variations during the H1N1 epidemic period.

Are organisations prepared for e-health implementation to respond to pandemic influenza?

E-health can facilitate communication and interactions among stakeholders involved in pandemic responses. Its implementation, nevertheless, represents a disruptive change in the healthcare workplace. Organisational preparedness assessment is an essential requirement prior to e-health implementation; including this step in the planning process can increase the chances of programme success. The objective of this study is to develop an e-health preparedness assessment model for pandemic influenza (EHPM4P). Following the Analytic Hierarchy Process (AHP), 20 contextual interviews were conducted with domain experts from May to September 2010. We examined the importance of all preparedness components within a fivedimensional hierarchical framework that was recently published. We also calculated the relative weight for each component at all levels of the hierarchy. This paper presents the hierarchical model (EHPM4P) that can be used to precisely assess healthcare organisational and providers' preparedness for e-health implementation and potentially maximise e-health benefits in the context of an influenza pandemic. Copyright © 2013 Inderscience Enterprises Ltd.

Computational analysis of proteome of H5N1 avian influenza virus to define T cell epitopes with vaccine potential

The existing vaccines against influenza are based on the generation of neutralizing antibody primarily directed against surface proteins-hernagglutinin and neuraminidase. In this work, we have computationally defined conserved T cell epitopes of proteins of influenza virus H5N1 to help in the design of a vaccine with haplotype specificity for a target population. The peptides from the proteome of H5NI irus which are predicted to bind to different HLAs, do not show similarity with peptides of human proteorne and are also identified to be generated by proteolytic cleavage. These peptides could be made use of in the design of either a DNA vaccine or a subunit vaccine against V influenza. (c) 2007 Elsevier Ltd. All rights reserved.

Structural analysis of the roles of influenza A virus membrane-associated proteins in assembly and morphology

The assembly of influenza A virus at the plasma membrane of infected cells leads to release of enveloped virions that are typically round in tissue culture-adapted strains but filamentous in strains isolated from patients. The viral proteins hemagglutinin (HA), neuraminidase (NA), matrix protein 1 (M1), and M2 ion channel all contribute to virus assembly. When expressed individually or in combination in cells, they can all, under certain conditions, mediate release of membrane-enveloped particles, but their relative roles in virus assembly, release, and morphology remain unclear. To investigate these roles, we produced membrane-enveloped particles by plasmid-derived expression of combinations of HA, NA, and M proteins (M1 and M2) or by infection with influenza A virus. We monitored particle release, particle morphology, and plasma membrane morphology by using biochemical methods, electron microscopy, electron tomography, and cryo-electron tomography. Our data suggest that HA, NA, or HANA (HA plus NA) expression leads to particle release through nonspecific induction of membrane curvature. In contrast, coexpression with the M proteins clusters the glycoproteins into filamentous membrane protrusions, which can be released as particles by formation of a constricted neck at the base. HA and NA are preferentially distributed to differently curved membranes within these particles. Both the budding intermediates and the released particles are morphologically similar to those produced during infection with influenza A virus. Together, our data provide new insights into influenza virus assembly and show that the M segment together with either of the glycoproteins is the minimal requirement to assemble and release membrane-enveloped particles that are truly virus-like.