Effectiveness of the Brazilian influenza vaccination policy, a systematic review

Since 1999, Brazil has undertaken annual influenza vaccine campaigns, free of charge, targeting the elderly population, health professionals, and immune-deficient patients. We conducted a systematic review of literature in order to evaluate the effectiveness of the initiative. We used the keywords influenza, vaccine, Brazil and effectiveness to search the main databases. Thirty-one studies matched our inclusion and exclusion criteria. Influenza vaccine coverage among the elderly is high, though not as high as suggested by the official figures. Estimates on effectiveness are scarce. The majority come from ecological studies that show a modest reduction in mortality and hospital admissions due to influenza-related causes. Such reduction is not evident in the North and Northeastern states of Brazil, a finding that is probably related to the different seasonal pattern of influenza in equatorial and tropical regions. Brazilian epidemiologists still owe society better-designed studies addressing the effectiveness of influenza vaccine campaigns.

Acellular and "low" pertussis vaccines: adverse events and the role of mutations

Objective: to discuss the current PAHO recommendation that does not support the substitution of traditional cellular DTP vaccine by acellular DTP, and the role of mutations, in humans, as the main cause of rare adverse events, such as epileptic-like convulsions, triggered by pertussis vaccine. Data review: the main components related to toxic effects of cellular pertussis vaccines are the lipopolysaccharide of bacterial cell wall and pertussis toxin. The removal of part of lipopolysaccharide layer has allowed the creation of a safer cellular pertussis vaccine, with costs comparable to the traditional cellular vaccine, and which may be a substitute for the acellular vaccine. Conclusion: The new methodology introduced by Instituto Butantan allows for the development of a new safer pertussis vaccine with low LPS content (Plow), and the use of the lipopolysaccharide obtained in the process in the production of monophosphoryl lipid A. This component has shown potent adjuvant effect when administered together with influenza inactivated vaccine, making possible to reduce the antigen dose, enhancing the production capacity and lowering costs.

Immune response to influenza vaccination in children treated with methotrexate or/and tumor necrosis factor-alpha inhibitors

In children treated with immunosuppressive medication such as methotrexate and tumor necrosis factor-alpha (TNF-α) inhibitors, additional immunizations are recommended because of increased susceptibility to infections. However, it is unclear if adequate antibody response to vaccinations can be established in children receiving methotrexate and/or TNF-α inhibitors. In a prospective open label study, we assessed seroprotection and seroconversion following influenza vaccination during 2 seasons (6 strains) in 36 children with autoimmune disease treated either with methotrexate (n=18), TNF-α inhibitors (n=10) or both (n=8) and a control group of 16 immunocompetent children. Influenza antibody titers were determined by hemagglutinin inhibition assay, before and 4-8 weeks after vaccination. Post-vaccination seroprotection (defined as a titer ≥1:40) did not significantly differ between immunosuppressed and immunocompetent subjects. Seroconversion, defined as the change from a nonprotective (< 1:40) to a protective titer (≥1:40) with at least a 4-fold titer increase, was less likely to occur in immunosuppressed patients, although no significant difference from the control group was established. Safety evaluation of vaccination showed no serious adverse events. Children receiving methotrexate and/or TNF-α inhibitors can be safely and effectively immunized against influenza, with a seroprotection after vaccination comparable to immunocompetent children.

Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines

Self-amplifying replicon RNA (RepRNA) are large molecules (12-14kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) - absolute requirements for vaccine design - were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo, inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines.

Biological and protective properties of immune sera directed to the influenza virus neuraminidase

The envelope of influenza A viruses contains two large antigens, hemagglutinin (HA) and neuraminidase (NA). Conventional influenza virus vaccines induce neutralizing antibodies that are predominantly directed to the HA globular head, a domain that is subject to extensive antigenic drift. Antibodies directed to NA are induced at much lower levels, probably as a consequence of the immunodominance of the HA antigen. Although antibodies to NA may affect virus release by inhibiting the sialidase function of the glycoprotein, the antigen has been largely neglected in past vaccine design. In this study, we characterized the protective properties of monospecific immune sera that were generated by vaccination with recombinant RNA replicon particles encoding NA. These immune sera inhibited hemagglutination in an NA subtype-specific and HA subtype-independent manner and interfered with infection of MDCK cells. In addition, they inhibited the sialidase activities of various influenza viruses of the same and even different NA subtypes. With this, the anti-NA immune sera inhibited the spread of H5N1 highly pathogenic avian influenza virus and HA/NA-pseudotyped viruses in MDCK cells in a concentration-dependent manner. When chickens were immunized with NA recombinant replicon particles and subsequently infected with low-pathogenic avian influenza virus, inflammatory serum markers were significantly reduced and virus shedding was limited or eliminated. These findings suggest that NA antibodies can inhibit virus dissemination by interfering with both virus attachment and egress. Our results underline the potential of high-quality NA antibodies for controlling influenza virus replication and place emphasis on NA as a vaccine antigen. IMPORTANCE The neuraminidase of influenza A viruses is a sialidase that acts as a receptor-destroying enzyme facilitating the release of progeny virus from infected cells. Here, we demonstrate that monospecific anti-NA immune sera inhibited not only sialidase activity, but also influenza virus hemagglutination and infection of MDCK cells, suggesting that NA antibodies can interfere with virus attachment. Inhibition of both processes, virus release and virus binding, may explain why NA antibodies efficiently blocked virus dissemination in vitro and in vivo. Anti-NA immune sera showed broader reactivity than anti-HA sera in hemagglutination inhibition tests and demonstrated cross-subtype activity in sialidase inhibition tests. These remarkable features of NA antibodies highlight the importance of the NA antigen for the development of next-generation influenza virus vaccines.

Use of intranet and other interventions to increase influenza vaccination among health care workers

Influenza (the flu) is a serious respiratory illness that can cause severe complications, often leading to hospitalization and even death. Influenza epidemics occur in most countries every year, usually during the winter months. Despite recommendations from the Centers for Disease Control and Prevention (CDC) and efforts by health care institutions across the United States, influenza vaccination rates among health care workers in the United States remain low. How to increase the number of vaccinated health care workers is an important public health question and is examined in two journal articles included here. ^ The first journal article evaluates the effectiveness of an Intranet intervention in increasing the proportion of health care workers (HCWs) who received influenza vaccination. Hospital employees were required go to the hospital's Intranet and select "vaccine received," "contraindicated," or "declined" from the online questionnaire. Declining employees automatically received an online pop-up window with education about vaccination; managers were provided feedback on employees' participation rates via e-mail messages. Employees were reminded of the Intranet requirement in articles in the employee newsletter and on the hospital's Intranet. Reminders about the Intranet questionnaire were provided through managers and newsletters to the HCWs. Fewer than half the employees (43.7%) completed the online questionnaire. Yet the hospital witnessed a statistically significant increase in the percentage of employees who received the flu vaccine at the hospital – 48.5% in the 2008-09 season as compared to 36.5%, 38.5% and 29.8% in the previous three years (P < 0.05). ^ The second article assesses current interventions employed by hospitals, health systems and nursing homes to determine which policies have been the most effective in boosting vaccination rates among American health care workers. A systematic review of research published between January 1994 and March 2010 suggests that education is necessary but not usually sufficient to increase vaccine uptake. Education about the flu and flu vaccines is most effective when complemented with easy access and making the vaccine free, although this combination may not be sufficient to achieve the desired vaccination levels among HCWs. The findings point toward adding incentives for HCWs to get vaccinated and requiring them to record their vaccination status on a declination/consent form – either written or electronic. ^ Based on these findings, American health care organizations, such as hospitals, nursing homes, and long-term care facilities, should consider using online declination forms as a method for increasing influenza vaccination rates among their employees. These online forms should be used in conjunction with other policies, including free vaccine, mobile distribution and incentives. ^ To further spur health care organizations to adopt policies and practices that will raise influenza vaccination rates among employees, The Joint Commission – an independent, not-for- profit organization that accredits and certifies more than 17,000 health care organizations and programs in the United States – should consider altering its standards. Currently, The Joint Commission does not require signed declination forms from employees who eschew vaccination; it only echoes the CDC's recommendations: "Health care facilities should require personnel who refuse vaccination to complete a declination form." Because participation in Joint Commission accreditation is required for Medicare reimbursement, action taken by the Joint Commission to require interventions such as mandatory declination/consent forms might result in immediate action by health care organizations to follow these new standards and lead to higher vaccination rates among HCWs.^ 1“Frequently Asked Questions for H1N1 and Seasonal Influenza.” The Joint Commission - Infection Control: http://www.jointcommission.org/PatientSafety/InfectionControl/h1n1_faq.htm. ^

Transloading of tumor cells with foreign major histocompatibility complex class I peptide ligand: a novel general strategy for the generation of potent cancer vaccines.

The major hurdle to be cleared in active immunotherapy of cancer is the poor immunogenicity of cancer cells. In previous attempts to overcome this problem, whole tumor cells have been used as vaccines, either admixed with adjuvant(s) or genetically engineered to express nonself proteins or immunomodulatory factors before application. We have developed a novel approach to generate an immunogeneic, highly effective vaccine: major histocompatibility complex (MHC) class I-positive cancer cells are administered together with MHC class I-matched peptide ligands of foreign, nonself origin, generated by a procedure we term transloading. Murine tumor lines of the H2-Kd or the H2-Db haplotype, melanoma M-3 and B16-F10, respectively, as well as colon carcinoma CT-26 (H2-Kd), were transloaded with MHC-matched influenza virus-derived peptides and applied as irradiated vaccines. Mice bearing a deposit of live M-3 melanoma cells were efficiently cured by this treatment. In the CT-26 colon carcinoma and the B16-F10 melanoma, high efficacies were obtained against tumor challenge, suggesting the universal applicability of this new type of vaccine. With foreign peptide ligands adapted to the requirements of a desired MHC class I haplotype, this concept may be used for the treatment of human cancers.

Similar antibody concentrations in Filipino infants at age 9 months, after 1 or 3 doses of an adjuvanted, 11-valent pneumoccoccal diphtheria/tetanus-Conjugated Vaccine: a randomized controlled trial

In Filipino infants, 1 dose of an adjuvanted, 11-valent pneumococcal conjugate vaccine (serotypes 1, 4, 5, 7F, 9V, 19F, and 23F conjugated to tetanus protein; and serotypes 3, 6B, 14, and 18C conjugated to diphtheria toxoid) administered alone at age 18 weeks (11PncTD1) elicited similar antibody concentrations at age 9 months as those elicited by 3 doses (11PncTD3) administered concomitantly with national program vaccines, at ages 6, 10, and 14 weeks. Geometric mean antibody concentrations ranged from 0.36 mug/mL ( for serotype 18C) to 5.81 mug/mL (for serotype 4), for the 11PncTD1 vaccine, and from 0.32 mug/mL (for serotype 18C) to 5.01 mug/mL (for serotype 19F), for the 11PncTD3 vaccine. The proportion of infants with threshold antibody concentrations greater than or equal to0.35 mug/mL was also similar (ranges, 55.6%-100% for the 11PncTD1 vaccine and 42.9%-100% for the 11PncTD3 vaccine). The functional activity of antibodies expressed as opsonophagocytic activity titers was similar in the 11PncTD1 and 11PncTD3 groups. This finding is an important one for countries with financial constraints and high pneumococcal disease burden.

Surfactant vesicle-mediated delivery of DNA vaccines via the subcutaneous route

Compared to naked DNA immunisation, entrapment of plasmid-based DNA vaccines into liposomes by the dehydration-rehydration method has shown to enhance both humoural and cell-mediated immune responses to encoded antigens administered by a variety of routes. In this paper we have compared the potency of lipid-based and non-ionic surfactant based vesicle carrier systems for DNA vaccines after subcutaneous immunisation. Plasmid pI.18Sfi/NP containing the nucleoprotein (NP) gene of A/Sichuan/2/87 (H3N2) influenza virus in the pI.18 expression vector was incorporated by the dehydration-rehydration method into various vesicle formulations. The DRV method, entailing mixing of small unilamellar vesicles (SUV) with DNA, followed by dehydration and rehydration, yielded high DNA vaccine incorporation values (85-97% of the DNA used) in all formulations. Studies on vesicle size revealed lipid-based systems formed cationic submicron size vesicles whilst constructs containing a non-ionic surfactant had significantly large z-average diameters (>1500 nm). Subcutaneous vesicle-mediated DNA immunisation employing two DRV(DNA) formulations as well as naked DNA revealed that humoural responses (immunoglobulin total IgG, and subclasses IgG 1 and 1gG 2a) engendered by the plasmid encoded nucleoprotein were substantially higher after dosing twice, 28 days apart with 10 μg DRV-entrapped DNA compared to naked DNA. Comparison between the lipid and non-ionic based vesicle formulations revealed no significant difference in stimulated antibody production. These results suggest that, not only can DNA be effectively entrapped within a range of lipid and non-ionic based vesicle formulations using the DRV method but that such DRV vesicles containing DNA may be a useful system for subcutaneous delivery of DNA vaccines. © 2004 Elsevier B.V. All rights reserved.

Efficacy, safety, and immunogenicity of the human papillomavirus 16/18 AS04-adjuvanted vaccine in women older than 25 years : 7-year follow-up of the phase 3, double-blind, randomised controlled VIVIANE study

Acknowledgments The VIVIANE study was funded and coordinated by GlaxoSmithKline Biologicals SA, which also covered all costs associated with development and publication of this report. We thank all study participants and their families. We gratefully acknowledge the work of the central and local study coordinators, and staff members of the sites who participated in this study. Writing support services were provided by Mary Greenacre (An Sgriobhadair, Isle of Barra, UK), on behalf of GSK Vaccines; editing and publication coordination services were provided by Jérôme Leemans (Keyrus Biopharma, Lasne, Belgium), Stéphanie Delval (XPE Pharma and Science, Wavre, Belgium), and Matthieu Depuydt (Business Decision Life Sciences, Brussels, Belgium), on behalf of GSK Vaccines

Seasonal influenza vaccine effectiveness in Portugal: results from the EuroEVA project 2015/16

The EuroEVA study aimed to estimate the 2015-16 end of season influenza vaccine effectiveness for all population and for the influenza vaccination target group. The presented results resulted from implementation of the study during 2015/2016 season.

Influenza vaccine effectiveness in Portugal: season 2015/2016 report

This report was prepared as part of the Project “Monitoring Influenza vaccine effectiveness during influenza seasons and pandemics in the European Union” and describes the results obtained in Portugal under the Protocol Agreement celebrated between EpiConcept SARL, Paris and National Health Institute Dr. Ricardo Jorge, Lisbon. Data and activities related to the individuals 65 years and more were funded by European Union’s Horizon 2020 research and innovation programme under grant agreement no 634446.

Modeling the impact of potential vaccines on epidemics of sexually transmitted chlamydia trachomatis infection

Background. We investigated the likely impact of vaccines on the prevalence of and morbidity due to Chlamydia trachomatis (chlamydia) infections in heterosexual populations. Methods.An individual‐based mathematical model of chlamydia transmission was developed and linked to the infection course in chlamydia‐infected individuals. The model describes the impact of a vaccine through its effect on the chlamydial load required to infect susceptible individuals (the “critical load”), the load in infected individuals, and their subsequent infectiousness. The model was calibrated using behavioral, biological, and clinical data. Results.A fully protective chlamydia vaccine administered before sexual debut can theoretically eliminate chlamydia epidemics within 20 years. Partially effective vaccines can still greatly reduce the incidence of chlamydia infection. Vaccines should aim primarily to increase the critical load in susceptible individuals and secondarily to decrease the peak load and/or the duration of infection in vaccinated individuals who become infected. Vaccinating both sexes has a beneficial impact on chlamydia‐related morbidity, but targeting women is more effective than targeting men. Conclusions.Our findings can be used in laboratory settings to evaluate vaccine candidates in animal models, by regulatory bodies in the promotion of candidates for clinical trials, and by public health authorities in deciding on optimal intervention strategies.

Pandemic (H1N1) 2009 Influenza Outbreak in Australia: Impact on Emergency Departments.

Executive summary Objective: The aims of this study were to identify the impact of Pandemic (H1N1) 2009 Influenza on Australian Emergency Departments (EDs) and their staff, and to inform planning, preparedness, and response management arrangements for future pandemics, as well as managing infectious patients presenting to EDs in everyday practice. Methods This study involved three elements: 1. The first element of the study was an examination of published material including published statistics. Standard literature research methods were used to identify relevant published articles. In addition, data about ED demand was obtained from Australian Government Department of Health and Ageing (DoHA) publications, with several state health departments providing more detailed data. 2. The second element of the study was a survey of Directors of Emergency Medicine identified with the assistance of the Australasian College for Emergency Medicine (ACEM). This survey retrieved data about demand for ED services and elicited qualitative comments on the impact of the pandemic on ED management. 3. The third element of the study was a survey of ED staff. A questionnaire was emailed to members of three professional colleges—the ACEM; the Australian College of Emergency Nursing (ACEN); and the College of Emergency Nursing Australasia (CENA). The overall response rate for the survey was 18.4%, with 618 usable responses from 3355 distributed questionnaires. Topics covered by the survey included ED conditions during the (H1N1) 2009 influenza pandemic; information received about Pandemic (H1N1) 2009 Influenza; pandemic plans; the impact of the pandemic on ED staff with respect to stress; illness prevention measures; support received from others in work role; staff and others’ illness during the pandemic; other factors causing ED staff to miss work during the pandemic; and vaccination against Pandemic (H1N1) 2009 Influenza. Both qualitative and quantitative data were collected and analysed. Results: The results obtained from Directors of Emergency Medicine quantifying the impact of the pandemic were too limited for interpretation. Data sourced from health departments and published sources demonstrated an increase in influenza-like illness (ILI) presentations of between one and a half and three times the normal level of presentations of ILIs. Directors of Emergency Medicine reported a reasonable level of preparation for the pandemic, with most reporting the use of pandemic plans that translated into relatively effective operational infection control responses. Directors reported a highly significant impact on EDs and their staff from the pandemic. Growth in demand and related ED congestion were highly significant factors causing distress within the departments. Most (64%) respondents established a ‘flu clinic’ either as part of Pandemic (H1N1) 2009 Influenza Outbreak in Australia: Impact on Emergency Departments. the ED operations or external to it. They did not note a significantly higher rate of sick leave than usual. Responses relating to the impact on staff were proportional to the size of the colleges. Most respondents felt strongly that Pandemic (H1N1) 2009 Influenza had a significant impact on demand in their ED, with most patients having low levels of clinical urgency. Most respondents felt that the pandemic had a negative impact on the care of other patients, and 94% revealed some increase in stress due to lack of space for patients, increased demand, and filling staff deficits. Levels of concern about themselves or their family members contracting the illness were less significant than expected. Nurses displayed significantly higher levels of stress overall, particularly in relation to skill-mix requirements, lack of supplies and equipment, and patient and patients’ family aggression. More than one-third of respondents became ill with an ILI. Whilst respondents themselves reported taking low levels of sick leave, respondents cited difficulties with replacing absent staff. Ranked from highest to lowest, respondents gained useful support from ED colleagues, ED administration, their hospital occupational health department, hospital administration, professional colleges, state health department, and their unions. Respondents were generally positive about the information they received overall; however, the volume of information was considered excessive and sometimes inconsistent. The media was criticised as scaremongering and sensationalist and as being the cause of many unnecessary presentations to EDs. Of concern to the investigators was that a large proportion (43%) of respondents did not know whether a pandemic plan existed for their department or hospital. A small number of staff reported being redeployed from their usual workplace for personal risk factors or operational reasons. As at the time of survey (29 October –18 December 2009), 26% of ED staff reported being vaccinated against Pandemic (H1N1) 2009 Influenza. Of those not vaccinated, half indicated they would ‘definitely’ or ‘probably’ not get vaccinated, with the main reasons being the vaccine was ‘rushed into production’, ‘not properly tested’, ‘came out too late’, or not needed due to prior infection or exposure, or due to the mildness of the disease. Conclusion: Pandemic (H1N1) 2009 Influenza had a significant impact on Australian Emergency Departments. The pandemic exposed problems in existing plans, particularly a lack of guidelines, general information overload, and confusion due to the lack of a single authoritative information source. Of concern was the high proportion of respondents who did not know if their hospital or department had a pandemic plan. Nationally, the pandemic communication strategy needs a detailed review, with more engagement with media networks to encourage responsible and consistent reporting. Also of concern was the low level of immunisation, and the low level of intention to accept vaccination. This is a problem seen in many previous studies relating to seasonal influenza and health care workers. The design of EDs needs to be addressed to better manage infectious patients. Significant workforce issues were confronted in this pandemic, including maintaining appropriate staffing levels; staff exposure to illness; access to, and appropriate use of, personal protective equipment (PPE); and the difficulties associated with working in PPE for prolonged periods. An administrative issue of note was the reporting requirement, which created considerable additional stress for staff within EDs. Peer and local support strategies helped ensure staff felt their needs were provided for, creating resilience, dependability, and stability in the ED workforce. Policies regarding the establishment of flu clinics need to be reviewed. The ability to create surge capacity within EDs by considering staffing, equipment, physical space, and stores is of primary importance for future pandemics.

Anticipated behaviours of emergency prehospital medical care providers during an influenza pandemic

Introduction: Emergency prehospital medical care providers are frontline health workers during emergencies. However, little is known about their attitudes, perceptions, and likely behaviors during emergency conditions. Understanding these attitudes and behaviors is crucial to mitigating the psychological and operational effects of biohazard events such as pandemic influenza, and will support the business continuity of essential prehospital services. ----- ----- Problem: This study was designed to investigate the association between knowledge and attitudes regarding avian influenza on likely behavioral responses of Australian emergency prehospital medical care providers in pandemic conditions. ----- ----- Methods: Using a reply-paid postal questionnaire, the knowledge and attitudes of a national, stratified, random sample of the Australian emergency prehospital medical care workforce in relation to pandemic influenza were investigated. In addition to knowledge and attitudes, there were five measures of anticipated behavior during pandemic conditions: (1) preparedness to wear personal protective equipment (PPE); (2) preparedness to change role; (3) willingness to work; and likely refusal to work with colleagues who were exposed to (4) known and (5) suspected influenza. Multiple logistic regression models were constructed to determine the independent predictors of each of the anticipated behaviors, while controlling for other relevant variables. ----- ----- Results: Almost half (43%) of the 725 emergency prehospital medical care personnel who responded to the survey indicated that they would be unwilling to work during pandemic conditions; one-quarter indicated that they would not be prepared to work in PPE; and one-third would refuse to work with a colleague exposed to a known case of pandemic human influenza. Willingness to work during a pandemic (OR = 1.41; 95% CI = 1.0–1.9), and willingness to change roles (OR = 1.44; 95% CI = 1.04–2.0) significantly increased with adequate knowledge about infectious agents generally. Generally, refusal to work with exposed (OR = 0.48; 95% CI = 0.3–0.7) or potentially exposed (OR = 0.43; 95% CI = 0.3–0.6) colleagues significantly decreased with adequate knowledge about infectious agents. Confidence in the employer’s capacity to respond appropriately to a pandemic significantly increased employee willingness to work (OR = 2.83; 95% CI = 1.9–4.1); willingness to change roles during a pandemic (OR = 1.52; 95% CI = 1.1–2.1); preparedness to wear PPE (OR = 1.68; 95% CI = 1.1–2.5); and significantly decreased the likelihood of refusing to work with colleagues exposed to (suspected) influenza (OR = 0.59; 95% CI = 0.4–0.9). ----- ----- Conclusions:These findings indicate that education and training alone will not adequately prepare the emergency prehospital medical workforce for a pandemic. It is crucial to address the concerns of ambulance personnel and the perceived concerns of their relationship with partners in order to maintain an effective prehospital emergency medical care service during pandemic conditions.