820 resultados para Adjuvanted Influenza Vaccines


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I Big Data stanno guidando una rivoluzione globale. In tutti i settori, pubblici o privati, e le industrie quali Vendita al dettaglio, Sanità, Media e Trasporti, i Big Data stanno influenzando la vita di miliardi di persone. L’impatto dei Big Data è sostanziale, ma così discreto da passare inosservato alla maggior parte delle persone. Le applicazioni di Business Intelligence e Advanced Analytics vogliono studiare e trarre informazioni dai Big Data. Si studia il passaggio dalla prima alla seconda, mettendo in evidenza aspetti simili e differenze.

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Influenza A virus is an important human pathogen causative of yearly epidemics and occasional pandemics. The ability to replicate within the host cell is a determinant of virulence, amplifying viral numbers for host-to-host transmission. This process requires multiple rounds of entering permissive cells, replication, and virion assembly at the plasma membrane, the site of viral budding and release. The assembly of influenza A virus involves packaging of several viral (and host) proteins and of a segmented genome, composed of 8 distinct RNAs in the form of viral ribonucleoproteins (vRNPs). The selective assembly of the 8-segment core remains one of the most interesting unresolved problems in virology. The recycling endosome regulatory GTPase Rab11 was shown to contribute to the process, by transporting vRNPs to the periphery, giving rise to enlarged cytosolic puncta rich in Rab11 and the 8 vRNPs. We recently reported that vRNP hotspots were formed of clustered vesicles harbouring protruding electron-dense structures that resembled vRNPs. Mechanistically, vRNP hotspots were formed as vRNPs outcompeted the cognate effectors of Rab11, the Rab11-Family-Interacting-Proteins (FIPs) for binding, and as a consequence impair recycling sorting at an unknown step. Here, we speculate on the impact that such impairment might have in host immunity, membrane architecture and viral assembly.

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Understanding how virus strains offer protection against closely related emerging strains is vital for creating effective vaccines. For many viruses, including Foot-and-Mouth Disease Virus (FMDV) and the Influenza virus where multiple serotypes often co-circulate, in vitro testing of large numbers of vaccines can be infeasible. Therefore the development of an in silico predictor of cross-protection between strains is important to help optimise vaccine choice. Vaccines will offer cross-protection against closely related strains, but not against those that are antigenically distinct. To be able to predict cross-protection we must understand the antigenic variability within a virus serotype, distinct lineages of a virus, and identify the antigenic residues and evolutionary changes that cause the variability. In this thesis we present a family of sparse hierarchical Bayesian models for detecting relevant antigenic sites in virus evolution (SABRE), as well as an extended version of the method, the extended SABRE (eSABRE) method, which better takes into account the data collection process. The SABRE methods are a family of sparse Bayesian hierarchical models that use spike and slab priors to identify sites in the viral protein which are important for the neutralisation of the virus. In this thesis we demonstrate how the SABRE methods can be used to identify antigenic residues within different serotypes and show how the SABRE method outperforms established methods, mixed-effects models based on forward variable selection or l1 regularisation, on both synthetic and viral datasets. In addition we also test a number of different versions of the SABRE method, compare conjugate and semi-conjugate prior specifications and an alternative to the spike and slab prior; the binary mask model. We also propose novel proposal mechanisms for the Markov chain Monte Carlo (MCMC) simulations, which improve mixing and convergence over that of the established component-wise Gibbs sampler. The SABRE method is then applied to datasets from FMDV and the Influenza virus in order to identify a number of known antigenic residue and to provide hypotheses of other potentially antigenic residues. We also demonstrate how the SABRE methods can be used to create accurate predictions of the important evolutionary changes of the FMDV serotypes. In this thesis we provide an extended version of the SABRE method, the eSABRE method, based on a latent variable model. The eSABRE method takes further into account the structure of the datasets for FMDV and the Influenza virus through the latent variable model and gives an improvement in the modelling of the error. We show how the eSABRE method outperforms the SABRE methods in simulation studies and propose a new information criterion for selecting the random effects factors that should be included in the eSABRE method; block integrated Widely Applicable Information Criterion (biWAIC). We demonstrate how biWAIC performs equally to two other methods for selecting the random effects factors and combine it with the eSABRE method to apply it to two large Influenza datasets. Inference in these large datasets is computationally infeasible with the SABRE methods, but as a result of the improved structure of the likelihood, we are able to show how the eSABRE method offers a computational improvement, leading it to be used on these datasets. The results of the eSABRE method show that we can use the method in a fully automatic manner to identify a large number of antigenic residues on a variety of the antigenic sites of two Influenza serotypes, as well as making predictions of a number of nearby sites that may also be antigenic and are worthy of further experiment investigation.

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Colibacillosis is a rather important economic problem for poultry production, associated to Avian Pathogenic Escherichia coli (APEC) strains, which may cause several extraintestinal pathologies, such as airsacculitis and cellulitis in broiler chickens, and salpingitis and peritonitis in broiler breeders, leading to septicemic mortality. Control of morbidity and mortality in the outbrakes of colibacillosis may be performed with antibiotics and/or by vaccination. The use antibiotics is frequently inef - fective as Escherichia coli ( E. coli ) is considered the largest reservoir of antimicrobial resistance, characteristic that may even transmit to other bacteria, turning the situation into a serious problem of public health. Vaccination may be the alternative solution but as many different strains arise, flock-specific autovaccines seem to be needed under several possible protocols, with live attenuated and/or inactivated vaccines from different strains that should be identified and characterized according to their virulence factors, within different flocks.

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Introduction: Paramedics and other emergency health workers are exposed to infectious disease particularly when undertaking exposure-prone procedures as a component of their everyday practice. This study examined paramedic knowledge of infectious disease aetiology and transmission in the pre-hospital care environment.--------- Methods: A mail survey of paramedics from an Australian ambulance service (n=2274) was conducted.--------- Results: With a response rate of 55.3% (1258/2274), the study demonstrated that paramedic knowledge of infectious disease aetiology and modes of transmission was poor. Of the 25 infectious diseases included in the survey, only three aetiological agents were correctly identified by at least 80% of respondents. The most accurate responses for aetiology of individual infectious diseases were for HIV/AIDS (91.4%), influenza (87.4%), and hepatitis B (85.7%). Poorest results were observed for pertussis, infectious mononucleosis, leprosy, dengue fever, Japanese B encephalitis and vancomycin resistant enterococcus (VRE), all with less than half the sample providing a correct response. Modes of transmission of significant infectious diseases were also assessed. Most accurate responses were found for HIV/AIDS (85.8%), salmonella (81.9%) and influenza (80.1%). Poorest results were observed for infectious mononucleosis, diphtheria, shigella, Japanese B encephalitis, vancomycin resistant enterococcus, meningococcal meningitis, rubella and infectious mononucleosis, with less than a third of the sample providing a correct response.--------- Conclusions: Results suggest that knowledge of aetiology and transmission of infectious disease is generally poor amongst paramedics. A comprehensive in-service education infection control programs for paramedics with emphasis on infectious disease aetiology and transmission is recommended.

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The development of chlamydial vaccines continues to be a major challenge for researchers. While acute infections are the main target of vaccine development groups, Chlamydia is well known for its ability to establish chronic or persistent infections in its host. To date, little effort has focussed specifically on the challenges of vaccines to successfully combat the chronic or persistent phase of the disease and yet this will be a necessary aspect of any fully successful chlamydial vaccine. This short review specifically examines the phenomenon of chlamydial persistence and the unique challenges that this brings to vaccine development.

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Aims: Influenza is commonly spread by infectious aerosols; however, detection of viruses in aerosols is not sensitive enough to confirm the characteristics of virus aerosols. The aim of this study was to develop an assay for respiratory viruses sufficiently sensitive to be used in epidemiological studies. Method: A two-step, nested real-time PCR assay was developed for MS2 bacteriophage, and for influenza A and B, parainfluenza 1 and human respiratory syncytial virus. Outer primer pairs were designed to nest each existing real-time PCR assay. The sensitivities of the nested real-time PCR assays were compared to those of existing real-time PCR assays. Both assays were applied in an aerosol study to compare their detection limits in air samples. Conclusions: The nested real-time PCR assays were found to be several logs more sensitive than the real-time PCR assays, with lower levels of virus detected at lower Ct values. The nested real-time PCR assay successfully detected MS2 in air samples, whereas the real-time assay did not. Significance and Impact of the Study: The sensitive assays for respiratory viruses will permit further research using air samples from naturally generated virus aerosols. This will inform current knowledge regarding the risks associated with the spread of viruses through aerosol transmission.

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In recent years the air transport industry has experienced unprecedented growth, driven by strong local and global economies. Whether this growth can continue in the face of anticipated oil crises; international economic forecasts and recent influenza outbreaks is yet to be seen. One thing is certain, airport owners and operators will continue to be faced with challenging environments in which to do business. In response, many airports recognize the value in diversifying their revenue streams through a variety of landside property developments within the airport boundary. In Australia it is the type and intended market of this development that is a point of contention between private airport corporations and their surrounding municipalities. The aim of this preliminary research is to identify and categorize on-airport development occurring at the twenty-two privatized Australian airports which are administered under the Airports Act [1996]. This new knowledge will assist airport and municipal planners in understanding the current extent and category of on-airport land use, allowing them to make better decisions when proposing development both within airport master plans and beyond the airport boundary in local town and municipal plans.

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Introduction: The core business of public health is to protect and promote health in the population. Public health planning is the means to maximise these aspirations. Health professionals develop plans to address contemporary health priorities as the evidence about changing patterns of mortality and morbidity is presented. Officials are also alert to international trends in patterns of disease that have the potential to affect the health of Australians. Integrated planning and preparation is currently underway involving all emergency health services, hospitals and population health units to ensure Australia's quick and efficient response to any major infectious disease outbreak, such as avian influenza (bird flu). Public health planning for the preparations for the Sydney Olympics and Paralympic Games in 2000 took almost three years. ‘Its major components included increased surveillance of communicable disease; presentations to sentinel emergency departments; medical encounters at Olympic venues; cruise ship surveillance; environmental and food safety inspections; bioterrorism surveillance and global epidemic intelligence’ (Jorm et al 2003, 102). In other words, the public health plan was developed to ensure food safety, hospital capacity, safe crowd control, protection against infectious diseases, and an integrated emergency and disaster plan. We have national and state plans for vaccinating children against infectious diseases in childhood; plans to promote dental health for children in schools; and screening programs for cervical, breast and prostate cancer. An effective public health response to a change in the distribution of morbidity and mortality requires planning. All levels of government plan for the public’s health. Local governments (councils) ensure healthy local environments to protect the public’s health. They plan parks for recreation, construct traffic-calming devices near schools to prevent childhood accidents, build shade structures and walking paths, and even embed drafts/chess squares in tables for people to sit and play. Environmental Health officers ensure food safety in restaurants and measure water quality. These public health measures attempt to promote the quality of life of residents. Australian and state governments produce plans that protect and promote health through various policy and program initiatives and innovations. To be effective, program plans need to be evaluated. However, building an integrated evaluation plan into a program plan is often forgotten, as planning and evaluation are seen as two distinct entities. Consequently, it is virtually impossible to measure, with any confidence, the extent to which a program has achieved its goals and objectives. This chapter introduces you to the concepts of public health program planning and evaluation. Case studies and reflection questions are presented to illustrate key points. As various authors use different terminology to describe the same concepts/actions of planning and evaluation, the glossary at the back of this book will help you to clarify the terms used in this chapter.

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In developed countries we once thought that the scourge of infectious diseases was tamed. Antibiotics were controlling infection in individual patients, vaccines were preventing illness and great faith was placed in the capacity of science to confound the most cunning organism. However, things have changed and in the new millennium we are confronting a host of challenges to public health from infectious diseases. Epidemics mean an excess of cases in the community from that normally expected or the appearance of a new infection (Webber ####, 22) Chapter 11 outlined the background to infectious diseases and the individual strategies directed towards the control and management of infectious diseases. The aim of this chapter is to outline the impact that infectious diseases have on population health, to identify the risks of major outbreaks and to identify the strategies required to reduce the risk and to manage any possible outbreak.

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In a randomized, double-blind study, 202 healthy adults were randomized to receive a live, attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and placebo 28 days apart in a cross-over design. A subgroup of 98 volunteers received a JE-CV booster at month 6. Safety, immunogenicity, and persistence of antibodies to month 60 were evaluated. There were no unexpected adverse events (AEs) and the incidence of AEs between JE-CV and placebo were similar. There were three serious adverse events (SAE) and no deaths. A moderately severe case of acute viral illness commencing 39 days after placebo administration was the only SAE considered possibly related to immunization. 99% of vaccine recipients achieved a seroprotective antibody titer ≥ 10 to JE-CV 28 days following the single dose of JE-CV, and 97% were seroprotected at month 6. Kaplan Meier analysis showed that after a single dose of JE-CV, 87% of the participants who were seroprotected at month 6 were still protected at month 60. This rate was 96% among those who received a booster immunization at month 6. 95% of subjects developed a neutralizing titer ≥ 10 against at least three of the four strains of a panel of wild-type Japanese encephalitis virus (JEV) strains on day 28 after immunization. At month 60, that proportion was 65% for participants who received a single dose of JE-CV and 75% for the booster group. These results suggest that JE-CV is safe, well tolerated and that a single dose provides long-lasting immunity to wild-type strains

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A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever (YF) vaccine (YF-17D strain; Stamaril(®), Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE virus strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.