Conserved HA-peptides expressed along with flagellin in Trichoplusia ni larvae protects chicken against intranasal H7N1 HPAIV challenge.

The immunization of poultry where H5 and H7 influenza viruses (IVs) are endemic is one of the strategies to prevent unexpected zoonoses. Our group has been focused on conserved HA-epitopes as potential vaccine candidates to obtain multivalent immune responses against distinct IV subtypes. In this study, two conserved epitopes (NG-34 and CS-17) fused to flagellin were produced in a Baculovirus platform based on Trichoplusia ni larvae as living biofactories. Soluble extracts obtained from larvae expressing "flagellin-NG34/CS17 antigen" were used to immunize chickens and the efficacy of the vaccine was evaluated against a heterologous H7N1 HPAIV challenge in chickens. The flagellin-NG34/CS17 vaccine protected the vaccinated chickens and blocked viral shedding orally and cloacally. Furthermore, no apparent clinical signs were monitored in 10/12 vaccinated individuals. The mechanism of protection conferred is under investigation.

Community's compliance with measures for the prevention of respiratory infections in Riyadh, Saudi Arabia.

BACKGROUND: Acute respiratory tract infections are the most common causes of both morbidity and mortality worldwid, and the management and prevention of acute respiratory infections is a global problem, especially in developing countries. This study sought to assess the community's compliance and practice of measures for the prevention of respiratory infections and discover their source of health information. MATERIALS AND METHODS: A cross-sectional study was carried out in the five biggest shopping malls in Riyadh city in July 2014. The required sample size was 980 persons aged 15 or older, with 196 from each of the five biggest shopping malls from each of the five geographic areas of Riyadh. Data was collected by face-to-face interview using standardised questionnaire, and analyzed using SPSS. RESULTS: Overall, 48.3% of the participants thought that they were susceptible to any of the respiratory infections of pandemic influenza; 59.7% always washed their hands with water and soap and 34.8% used antibacterial soap. About 29% reported avoiding touching their eyes, noses, and mouths directly with their hands; 63.5% covered their noses and mouths with tissue paper when sneezing or coughing. A substantial number said they "never" shared their personal stuff, including towels (70.5%) and utensils (49.0%) with others. Only 21.2% avoided crowded places or wore a mask (9.1%) in such a situation. A high proportion (62.8%) did not take the seasonal flu vaccine. The most common sources of health information included television/radio (47.9%), social media (29.4%), and friends/family (28.1%). CONCLUSIONS: Health authorities should seize every opportunity to prevent respiratory infections by adopting all evidence-based infection control measures to improve public awareness, attitude, and practice.

A nanoemulsion-adjuvanted intranasal H5N1 influenza vaccine protects ferrets against homologous and heterologous H5N1 lethal challenge.

BACKGROUND: Flu vaccines administered intramuscularly (IM) have shown seasonally fluctuating efficacy, 20-60%, throughout the last 15 years. We formulated a recombinant H5 (rH5) in our Nanovax® (NE01) (rH5/NE01) adjuvant for intranasal vaccination in ferrets. We evaluated the regimen, one vs two immunization, and cross clade protection a ferret challenge model. METHODS: Plant derived recombinant H5 (rH5) antigen was formulated with NE01 and administered intranasally to ferrets. Immunogenicity (IgG), hemagglutination inhibition (HI), and protection against lethal challenge, were measured following one or two immunizations. Protection against homologous (strain A/Indo) and heterologous (strain A/Vn) was evaluated in ferrets following two immunizations. RESULTS: IN immunization with rH5/NE01 induced significant IgG levels after one and two immunizations. One vaccination did not induce any HI while low HI was measured after two immunizations. Homologous challenge with H5N1 A/ Indonesia showed 100% survival, with minimal weight loss in animals vaccinated twice compared to the unvaccinated controls. Analysis of nasal wash from these challenged ferrets vaccinated twice showed decreased viral shedding compared to unvaccinated controls. Interestingly, animals that received one vaccination showed 88% survival with moderate weight loss. Cross clade protection was evaluated using an increased antigen dose (45 µg rH5). Vaccinated animals demonstrated increased IgG and HAI antibody responses. Both homologous (A/Indo) and heterologous challenge (A/Vietnam) following two immunizations showed 100% survival with no loss of body weight. However viral clearance was more rapid against the homologous (day 3) compared to the heterologous (day 5) post challenge. CONCLUSION: Intranasal administration of NE01 adjuvant-formulated rH5 vaccine elicited systemic and probably mucosal immunity that conferred protection against lethal challenge with homologous or heterologous viral strains. It also enhanced viral clearance with decreased shedding. These outcomes strongly suggest that intranasal immunization using NE01 against flu infections warrants clinical testing.

Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in adults 65years of age and older: A phase II, observer-blind, randomized, controlled trial.

BACKGROUND: H7 influenza strains can cause severe and often fatal human infections, especially in the elderly. This phase II, observer-blind, randomized trial (www.ClinicalTrials.gov: NCT01949090) assessed the immunogenicity and safety of a novel AS03-adjuvanted H7N1 vaccine that may serve as a model H7-subtype vaccine. METHODS: 360 adults ≥65years of age in stable health received either 1 of 4 adjuvanted A/mallard/Netherlands/12/2000 split virion vaccine formulations (3.75µg or 7.5µg hemagglutinin adjuvanted with either AS03A or AS03B) or saline placebo, given as a 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays for the per-protocol cohort, comprising 332 participants at 21days post-each dose, 332 at month 6, and 309 at month 12 (HI assay only). Safety was assessed up to month 12 for all participants who had received ≥1 dose (360 participants). RESULTS: For H7N1 HI antibody assessment at day 42 (21days post-dose 2), seroprotection rates (SPR) in the vaccinated groups were 69.6%-88.7%, seroconversion rates (SCR) 69.6%-88.5%, mean geometric increase (MGI) 11.0-18.9, and HI geometric mean titers (GMTs) 55.0-104.8. These parameters declined by month 6 and month 12. Microneutralization GMTs were 46.2-74.7 in the vaccinated groups at day 42, while vaccine response rate (VRR; proportion with ≥4-fold increase in MN titer) was 46.4%-81.5%. For the cross-reactive H7N9 strain, at day 42, HI GMT were 64.3-201.3, SPR 78.6%-96.3%, SCR 79.3%-96.3%, and MGI 14.1-37.7; MN GMTs were 44.0-85.6, and VRR 46.4-85.2%. The most frequent solicited symptom was injection site pain (41.7%-65.0% of vaccine recipients). In total, 40 participants reported 67 serious adverse events; none were considered causally related to vaccination. CONCLUSIONS: In adults aged ≥65years, the adjuvanted H7N1 vaccine was immunogenic after 2 doses, and had an acceptable safety profile. www.ClinicalTrials.gov: NCT01949090.

Immunogenicity and safety of an AS03-adjuvanted H7N1 vaccine in healthy adults: A phase I/II, observer-blind, randomized, controlled trial.

BACKGROUND: H7 influenza strains have pandemic potential. AS03-adjuvanted H7N1 A/mallard/Netherlands/12/2000 split-virion vaccine formulations were evaluated as model H7-subtype vaccine and tested after H7N9 emerged in China, and caused severe human disease with high mortality. METHODS: In this phase I/II, observer-blind, randomized trial in US and Canada, 420 healthy adults (21-64years) were randomized to receive 1 of 4 H7N1 vaccine formulations (3.75 or 7.5µg hemagglutinin adjuvanted with either AS03A or AS03B), 15µg unadjuvanted H7N1 hemagglutinin, or saline placebo, given as 2-dose series. Immunogenicity was assessed using hemagglutination-inhibition (HI) and microneutralization (MN) assays, at day 42 (21days post-dose 2), month 6, and month 12 (HI only) for the per-protocol cohorts (398, 379 and 368 participants, respectively). Safety is reported up to month 12. RESULTS: Beneficial AS03 adjuvant effect was demonstrated. Committee for Medical Products for Human Use, and Center for Biologics Evaluation and Research (CBER) criteria were met for all adjuvanted formulations at day 42 (H7N1 HI assay); seroprotection (SPR) and seroconversion rates (SCR) were 88.5-94.8%, mean geometric increase (MGI) 19.2-34.9, and geometric mean titers (GMT) 98.3-180.7. Unadjuvanted H7N1 vaccine did not meet CBER criteria. In adjuvanted groups, antibody titers decreased over time; month 12 SPRs and GMTs were low (2.0-18.8% and 8.1-12.2). MN antibodies showed similar kinetics, with titers persisting at higher range than HI at month 6. All adjuvanted groups showed cross-reactivity against H7N9, with HI responses similar to H7N1. The most frequent solicited symptom in adjuvanted groups was injection site pain (71.2-86.7%); grade 3 solicited symptoms were infrequent. Nine participants reported 17 serious adverse events; none were considered causally related to vaccination. CONCLUSIONS: Adjuvanted H7N1 vaccine formulations had an acceptable safety profile and induced an antibody response after 2 doses with cross-reactivity to H7N9. ClinicalTrials.gov: NCT01934127.

Rethinking the antivaccine movement concept: A case study of public criticism of the swine flu vaccine's safety in France.

In this article I discuss the definition of "the Antivaccine Movement" using the case of the French controversy over the safety of the 2009 pandemic flu vaccine. I show that the group of main actors who criticized the vaccine's safety is heterogeneous. This heterogeneity can be found in the type of arguments mobilized to question the vaccine's safety and in these actors' likelihood of being involved in any vaccine-related controversies. I show that only a minority of these actors rejected vaccination in general and mobilized against all vaccination campaigns. Most of these actors only occasionally mobilized against a given vaccine or vaccination campaign and they did so to promote a political or cultural agenda that went beyond the vaccine itself. Using these results, I argue that in order to better understand how vaccine-related controversies emerge and why some activists devote time and resources to spread vaccine-critical arguments, social scientists should use three distinct concepts to refer to vaccine criticism: The Antivaccine Movement, the Marginally Antivaccine Movements and the Occasionally Vaccine Critical Movements. To do so would enable social scientists and public health experts to better understand the different ways in which vaccination can become politicized and the evolution of this politicization.

Flu Vaccination: The Gap Between Evidence and Public Policy.

The research presented in this article exposes a wide gap between evidence and public policy with regard to influenza vaccination in the context of the 2009 pandemic and with regard to yearly seasonal epidemics. It shows that the World Health Organization and health authorities worldwide failed to protect the interests of the most vulnerable during the 2009 flu pandemic and demonstrates a lack of scientific base for seasonal flu vaccination campaigns. Narrowing the gap between scientific evidence and public health policies with regard to influenza is a serious and urgent matter, one that implies confronting the interests of big pharmaceutical corporations and their allies at academic and government levels. The credibility of science and the well-being of many are at stake.

Factors influencing school closure and dismissal decisions: influenza A (H1N1), Michigan 2009.

BACKGROUND: In fall 2009, many US communities experienced school closures during the influenza A H1N1 pandemic (pH1N1) and the state of Michigan reported 567 closures. We conducted an investigation in Michigan to describe pH1N1-related school policies, practices, and identify factors related to school closures. METHODS: We distributed an online survey to all Michigan K-12 school principals. Descriptive statistics and chi-square tests summarize school policies, practices, adherence to government guidelines, and differences between schools that closed and those that remained open during the pandemic. RESULTS: Of 4441 traditional K-12 Michigan schools, 937 (21%) principals responded to our survey representing approximately 374,000 students and 17,700 teachers. The majority (88%) of schools had influenza preparedness plans and followed government school influenza guidelines. Among respondents, 15% (137/937) of schools closed in fall 2009 with high absenteeism as the primary reason for closure. Schools that closed reported significant illness in their school, had <300 students, and had invested substantial resources preparing and responding to influenza. CONCLUSIONS: Adherence to government guidelines for schools appears high in Michigan. Closures occurred in schools that reported significant illness and were likely motivated by excessive absenteeism. Understanding factors related to closures during pH1N1 may inform future pandemic preparedness efforts.

Clinical Outcome of Novel H1N1 (Swine Flu)-Infected Patients During 2009 Pandemic at Tertiary Referral Hospital in Western India.

BACKGROUND: The first case of 2009 pandemic influenza A (H1N1) virus in Gujarat, India, was reported in August 2009. Oseltamivir was used for treatment of pandemic influenza in India. We discuss the clinical characteristics and outcome of the hospitalized patients with H1N1 infection during 2009 pandemic influenza season. MATERIALS AND METHODS: Hospitalized patient with laboratory-confirmed H1N1 flu during August 2009 to February 2010 were included in this retrospective study. Data were collected from hospital ICU charts. Patients discharged from hospital were considered cured from swine flu. Data analysis was performed using CDC software EPI Info v3.5.3. Both univariate and multivariate analyses were conducted. RESULTS: A total of 63 patients were included in the study, of them 41 (65%) males and 22 (35%) females. Median age was 34 (3-69) years and median duration of symptoms before hospitalization was 5 (2-20) days. Common presenting symptoms include fever 58 (92.06%), cough 58 (92.06%), breathlessness 38 (60.31%), common cold 14 (22.22%), vomiting 12 (19.04%), weakness 9 (14.28%), throat pain 7 (11.11%), body ache 5 (7.93%), and chest pain 4 (6.34%). Co-morbidities were seen in 13 (20.63%) patients. Steroids were used in 39 (61.90%) patients, and ventilatory support was required in 17 (26.98%) patients. On presentation chest x-ray was normal in 20 (31.74%) patients, while pulmonary opacities were seen in 43 (68.26%) patients. Forty-seven (74.60%) patients were cured and discharged from hospital, 14 (22.22%) patients died, and 2 (3.17%) patients were shifted to other hospital. Ventilatory requirement, pneumonia, and co-morbidities were the independent predictors of mortality, while age, sex, and steroid use were not associated with increased mortality. CONCLUSION: 2009 pandemic influenza A had the same clinical features as seasonal influenza except vomiting. Mortality rate was high in 2009 H1N1-infected patients with pneumonia, co-morbid conditions, and patients who required ventilatory support.

Who is willing to risk his life for a patient with a potentially fatal, communicable disease during the peak of A/H1N1 pandemic in Israel?

BACKGROUND: The willingness of healthcare workers to risk their lives for a patient with a potentially fatal, communicable disease is a major concern, especially during a pandemic where the need for adequate staffing is crucial and where the public atmosphere might enhance anxiety and fear of exposure. OBJECTIVE: To examine the relationships between the willingness of healthcare workers to risk their lives for a patient with a potentially fatal A/H1N1 flu, and knowledge of personal protection against infection, and trust in colleagues, workplace preparedness and the effectiveness of safety measures, during the winter A/H1N1 pandemic in Israel. MATERIALS AND METHODS: A questionnaire was distributed to healthcare workers in 21 hospitals in Israel between 26 November 2009 and 10 December 2009 (the peak of the winter A/H1N1 flu outbreak). The questionnaire was completed by 1147 healthcare workers. RESULTS: Willingness to risk one's life for a patient was significantly lower in females, respondents of younger age (18-24 years), administrative staff, and those with a non-academic education, as well as among those with a less knowledge about safety measures and among those with less trust in colleagues, in work place preparedness, and in the effectiveness of safety measures. CONCLUSIONS: Willingness to risk one's life for a patient is related to knowledge of safety measures, and trust in colleagues and work place preparedness. Education programs to enhance trust in colleagues, improve work place preparedness, and safety measures are recommended, especially for healthcare workers who are young, inexperienced, female, or administrative staff.

Análisis de concordancia de cuatro pruebas rápidas para la detección de influenza A en Bogotá / Analysis of concordance of four rapid diagnostic tests for influenza A detection in Bogota-Colombia

La rapidez, eficacia y oportunidad del diagnóstico de influenza facilita el manejo de casos confirmados a nivel terapéutico más aun considerándose el estado actual del virus pandémico H1N1/2009. Objetivo: Analizar la concordancia de cuatro pruebas rápidas para la detección de Influenza A en Bogotá. Métodos: En este estudio descriptivo de corte transversal fueron comparadas cuatro pruebas rápidas para la detección de Influenza A (Quick Vue Influenza A+B; Directigen Ez Flu A+B®; SD Bioline Influenza Antigen® y Clearview Exact Influenza A and B®) en un grupo de 57 hisopados nasofaríngeos de pacientes sospechosos del virus pandémico H1N1/2009, los cuales fueron analizados previamente por PCR en tiempo real y clasificados como positivos o negativos para Influenza A. Resultados: El comportamiento de las pruebas rápidas valorado por su concordancia global con la prueba de referencia fluctuó entre 68,19% y 74,47%, sin evidencias de diferencias estadísticamente significativa entre ellas (c2=0,35; p=0,95). Tampoco se encontró un comportamiento diferencial estadísticamente significativo al valorar la proporción de concordancia entre los positivos de cada una de las pruebas rápidas con la prueba de referencia. Conclusión: Existen varios trabajos a favor y en contra de las pruebas rápidas para influenza, y algunos destacan su baja sensibilidad y especificidad comparadas con otras metodologías, como inmunofluorescencia directa, cultivo viral y RT-PCR. Sin embargo,ante la emergencia que actualmente se vive por la pandemia viral H1N1/2009, diferentes estrategias de vigilancia en salud pública, incluidas los estudios centinela y de conglomerados, pudieran ser implementados y las pruebas rápidas influenza (sin importar la casa comercial) serían útiles por sus características operativas, bajo costo y la posibilidad de lograr mayores coberturas de identificación de casos nuevos, descongestión de servicio y ajuste rápido de medidas en salud pública.

Rapidity, effectiveness and opportunity of influenza diagnosis make easy confirmed cases handling at therapeutic level most of all considering actual state of pandemic virus A H1N1/2009. Objective: To analyze agreement of four quick tests for Influenza A detection of in Bogotá. Methods: In a cross sectional fashion it was compared four quick tests designed for influenza detection (Quick Vue Influenza A + B; Directigen Ez Flu A + B®; SD Bioline Influenza Antigen® and Clearview Exact Influenza A and B®) in 57 nasopharynxeal hyssoped examples of suspicious patients of pandemic A H1N1/2009 virus, all of them were previously analyzed by real-time PCR and classified as positive for that virus. Results: Behavior of fast tests valued by its global agreement against test of reference fluctuated between 68.19% and 74,47%, without significant statistical differences among them (p=0,95). Neither significant statistical differences were found upon valuing proportion of agreement among positives each one of fast tests with reference test. Conclusions: There are some works on behalf or against of influenza rapid tests, and some of them emphasizes their low sensibility and specificity against other techniques, like direct inmunofluorescence inmunofluorescence, viral culture and RT-PCR. Nevertheless, in order to face the actual viral AH1N1/2009 pandemic, different strategies of public health surviellance, (including sentinel and conglomerate studies), could be implemented. Influenze Rapid tests (making exclusion of trade mark) would be serviceable by their operative characteristics, low cost and high possibility of identify new cases and by that way, it would possible emergence services decongestion and fast adjustment of measures in Public Health.