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Influenza A viruses (IAV) are fast-evolving pathogens with a very high mutation rate (2.0 × 10-6 to 2.0 × 10-4) compared to the influenza B (IBV) and influenza C (ICV) viruses. Generally, the tropical regions are considered as the reservoir for the IAV's genetic and antigenic evolutionary modification to be reintroduced into the temperate region. Therefore, in connection to the above facts, the present study emphasized on the evolutionary dynamic of the pandemic-2009 H1N1 (pdmH1N1) influenza virus in India. A total of Ninety-two whole genome sequences of pdmH1N1 viruses circulating in India during the 2009 post-pandemic era were analysed. The temporal signal of the study, indicating strict molecular clock evolutionary process and the overall substitution rate is 2.21 × 10-3/site/year. We are using the nonparametric Bayesian Skygrid coalescent model to estimates the effective past population dynamic or size over time. The study exhibits a strong relation between the genetic distances and collection dates of the Indian pdmH1N1 strain. The skygrid plot represents the highest exponential growth of IAV in rainy and winter seasons. All the genes of Indian pdmH1N1 were under purifying selective pressure. The Bayesian time-imprinted phylogenetic tree represents the following clade distributions in the country within the last 10 years; I) clade 6, 6C, and 7 were co-circulating between the 2011 to 2012 flu season; II) the clade 6B was introduced into circulation in the late seasons of 2012; III) lastly, the clade 6B remain existing in the circulation and segregated into subclade 6B.1 with five different subgroup (6B.1A, 6B.1A.1, 6B.1A.5a, 6B.1A.5a.2, 6B.1A.7). The recent circulating strain of Indian H1N1 strain represent the insertion of basic-amino acid arginine (R) in the cleavage site (325/K-R) of HA protein and amino acid mutation (314/I-M) on the lateral head surface domain of NA protein. Moreover, the study indicates the sporadic presence of the oseltamivir-resistant (275/H-Y) H1N1 variant in circulation. The present study suggests the purifying selective pressure and stochastic ecological factors for the existence and adaptation of a certain clade 6B in the host populations and additional information on the emergence of mutated strains in the circulation.
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Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Filogenia , Teorema de Bayes , Análisis de Secuencia de ADN , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Neuraminidasa/genética , Virus de la Influenza A/genética , India/epidemiologíaRESUMEN
BACKGROUND: Lymphopenia has been observed in severe pandemic influenza A/H1N1 in developed countries. However, data from developing countries are rare and dynamic change of lymphocyte counts in severe pandemic influenza A/H1N1 is scarcely reported. This study aimed to observe change of lymphocyte counts in patients with severe pandemic influenza A/H1N1 and to investigate the correlation of lymphopenia and severe pandemic influenza A/H1N1. METHODS: We retrospectively analyzed the white blood cell counts and differentials and other clinical data in 21 hospitalized patients with severe pandemic influenza A/H1N1 confirmed by reverse-transcription PCR during 2009 and 2010. RESULTS: All patients, except two cases with bacterial co-infections, had normal or reduced white blood cell counts. Seventeen (81.0%) patients had decreased lymphocyte proportions (<20%) and counts (<0.8×109/L), with the lowest value of 1.2% and 0.1×109/L respectively. A patient with nosocomial infection of influenza A/H1N1 showed that lymphopenia occurred on the first day of illness. Lymphocyte proportions and absolute counts returned to normal or slightly higher than normal in 16 of the 17 patients within 2-3weeks after the disease onset. CONCLUSIONS: Lymphopenia along with other clinical parameters may be helpful in early differential diagnosis of severe pandemic influenza A/H1N1.
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Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/complicaciones , Gripe Humana/patología , Recuento de Linfocitos , Linfocitos/inmunología , Linfopenia/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The pandemic influenza A (H1N1) virus has spread worldwide and infected a large proportion of the human population. Discovery of new and effective drugs for the treatment of influenza is a crucial issue for the global medical community. According to our previous study, TSL-1, a fraction of the aqueous extract from the tender leaf of Toonasinensis, has demonstrated antiviral activities against pandemic influenza A (H1N1) through the down-regulation of adhesion molecules and chemokine to prevent viral attachment. METHODS: The aim of the present study was to identify the active compounds in TSL-1 which exert anti-influenza A (H1N1) virus effects. XTT assay was used to detect the cell viability. Meanwhile, the inhibitory effect on the pandemic influenza A (H1N1) virus was analyzed by observing plaque formation, qRT-PCR, neuraminidase activity, and immunofluorescence staining of influenza A-specific glycoprotein. RESULTS: Both catechin and gallic acid were found to be potent inhibitors in terms of influenza virus mRNA replication and MDCK plaque formation. Additionally, both compounds inhibited neuraminidase activities and viral glycoprotein. The 50% effective inhibition concentration (EC50) of catechin and gallic acid for the influenza A (H1N1) virus were 18.4 µg/mL and 2.6 µg/mL, respectively; whereas the 50% cytotoxic concentrations (CC50) of catechin and gallic acid were >100 µg/mL and 22.1 µg/mL, respectively. Thus, the selectivity indexes (SI) of catechin and gallic acid were >5.6 and 22.1, respectively. CONCLUSION: The present study demonstrates that catechin might be a safe reagent for long-term use to prevent influenza A (H1N1) virus infection; whereas gallic acid might be a sensitive reagent to inhibit influenza virus infection. We conclude that these two phyto-chemicals in TSL-1 are responsible for exerting anti-pandemic influenza A (H1N1) virus effects.
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Antivirales/farmacología , Catequina/farmacología , Ácido Gálico/farmacología , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Células A549 , Animales , Perros , Humanos , Subtipo H1N1 del Virus de la Influenza A/fisiología , Células de Riñón Canino Madin Darby , Replicación Viral/efectos de los fármacosRESUMEN
Abstract Objective To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. Methods Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. Results SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). Conclusion The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients.
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The kinetics, longevity, and breadth of antibodies to influenza virus neuraminidase (NA) in archival, sequential serum/plasma samples from influenza A virus (IAV) H5N1 infection survivors and from patients infected with the 2009 pandemic IAV (H1N1) virus were determined using an enzyme-linked lectin-based assay. The reverse-genetics-derived H4N1 viruses harboring a hemagglutinin (HA) segment from A/duck/Shan Tou/461/2000 (H4N9) and an NA segment derived from either IAV H5N1 clade 1, IAV H5N1 clade 2.3.4, the 2009 pandemic IAV (H1N1) (H1N1pdm), or A/Puerto Rico/8/1934 (H1N1) virus were used as the test antigens. These serum/plasma samples were also investigated by microneutralization (MN) and/or hemagglutination inhibition (HI) assays. Neuraminidase-inhibiting (NI) antibodies against N1 NA of both homologous and heterologous viruses were observed in H5N1 survivors and H1N1pdm patients. H5N1 survivors who were never exposed to H1N1pdm virus developed NI antibodies to H1N1pdm NA. Seroconversion of NI antibodies was observed in 65% of the H1N1pdm patients at day 7 after disease onset, but an increase in titer was not observed in serum samples obtained late in infection. On the other hand, an increase in seroconversion rate with the HI assay was observed in the follow-up series of sera obtained on days 7, 14, 28, and 90 after infection. The study also showed that NI antibodies are broadly reactive, while MN and HI antibodies are more strain specific.
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Anticuerpos Antivirales/sangre , Reacciones Cruzadas , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Neuraminidasa/inmunología , Seroconversión , Proteínas Virales/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Pruebas de Inhibición de Hemaglutinación/métodos , Humanos , Masculino , Pruebas de Neutralización , Factores de Tiempo , Adulto JovenRESUMEN
Influenza A virus remains a major threat to public health, and the inactivated split-virus vaccine is the most prevalent vaccine used worldwide. However, our knowledge about cellular immune responses to the inactivated influenza virus vaccine and its correlation with humoral responses are yet limited, which has restricted our understanding of the vaccine's protective mechanisms. Herein, in two clinical trials, T-cell responses specific for both previously identified human leucocyte antigen (HLA)-I-restricted epitopes from influenza virus and hemagglutinin (HA) protein were longitudinally investigated before, during, and after a two-dose vaccination with the inactivated 2009 pandemic H1N1 (2009-pH1N1) vaccine. A robust antibody response in all of the donors after vaccination was observed. Though no CD8+ T-cell responses to known epitopes were detected, HA-specific T-cell responses were primed following vaccination, and the responses were found to be mainly CD4+ T-cell dependent. However, HA-specific T-cells circulating in peripheral blood dropped to baseline levels 6weeks after vaccination, but humoral immune responses maintained a high level for 4months post-vaccination. Significant correlations between the magnitude of the HA-specific T-cell responses and hemagglutination inhibition antibody titers were demonstrated, indicating a priming role of HA-specific T-cells for humoral immune responses. In conclusion, our study indicates that HA-specific CD4+ T-cell responses can be primed by the inactivated 2009-pH1N1 vaccine, which may coordinate with the elicitation of antibody protection. These findings would benefit a better understanding of the immune protective mechanisms of the widely used inactivated 2009-pH1N1 vaccine.
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Linfocitos T CD4-Positivos/inmunología , Hemaglutininas/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Vacunas de Productos Inactivados/inmunología , Adolescente , Adulto , Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Femenino , Pruebas de Inhibición de Hemaglutinación/métodos , Humanos , Masculino , Persona de Mediana Edad , Vacunación , Adulto JovenRESUMEN
PURPOSE: We aimed at investigating whether, in Germany, the number of individual case safety reports (ICSR) of confirmed narcolepsy following Pandemrix® vaccination notified to the Paul-Ehrlich-Institut (PEI, German Federal Institute for Vaccines and Biomedicines) was higher than expected when compared with the prepandemic background incidence rates. METHODS: ICSR of narcolepsy after vaccination with Pandemrix® notified to the PEI until September 2016 were reviewed and validated according to the criteria of narcolepsy defined by the Brighton Collaboration (BC). Cases fulfilling the criteria of BC levels of diagnostic certainty 1 to 4a with symptoms onset after vaccination with Pandemrix® were eligible. Adjustment for underreporting was performed with cases of narcolepsy recruited within the scope of the German Narcolepsy Study using capture-recapture methods. An observed versus expected (OvE) analysis was conducted based on adjusted case numbers using risk windows for symptoms onset within 4 and 6 months following vaccination. RESULTS: By the end of September 2016, a total of 85 ICSR of narcolepsy after vaccination with Pandemrix® had been notified to the PEI 52 of which were eligible. The OvE estimates for the 4 and 6 months risk windows were 3.8 (95% CI: 2.6-5.4) and 2.8 (95% CI: 2.0-3.9), respectively. The number of excess cases was higher in children and adolescents (15-fold and 11.7-fold increased OvE estimate) than in adults (2.1-fold and 1.5-fold increased estimate). CONCLUSIONS: Compared with the prepandemic background incidence rate, the number of incident narcolepsy cases was 3.8-fold and 2.8-fold as high.
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Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza/efectos adversos , Narcolepsia/inducido químicamente , Narcolepsia/epidemiología , Adolescente , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Factores de Edad , Estudios de Casos y Controles , Niño , Métodos Epidemiológicos , Femenino , Alemania/epidemiología , Humanos , Incidencia , Recién Nacido , Masculino , Persona de Mediana Edad , Narcolepsia/psicología , Medición de Riesgo , Seguridad , Vacunación/efectos adversos , Vacunación/estadística & datos numéricosRESUMEN
OBJECTIVE: Studies associate pandemic influenza vaccination with narcolepsy. In Germany, a retrospective, multicenter, matched case-control study was performed to identify risk factors for narcolepsy, particularly regarding vaccinations (seasonal and pandemic influenza vaccination) and infections (seasonal and pandemic influenza) and to quantify the detected risks. METHODS: Patients with excessive daytime sleepiness who had been referred to a sleep center between April 2009 and December 2012 for multiple sleep latency test (MSLT) were eligible. Case report forms were validated according to the criteria for narcolepsy defined by the Brighton Collaboration (BC). Confirmed cases of narcolepsy (BC level of diagnostic certainty 1-4a) were matched with population-based controls by year of birth, gender, and place of residence. A second control group was established including patients in whom narcolepsy was definitely excluded (test-negative controls). RESULTS: A total of 103 validated cases of narcolepsy were matched with 264 population-based controls. The second control group included 29 test-negative controls. A significantly increased odd ratio (OR) to develop narcolepsy (crude OR [cOR] = 3.9, 95% confidence interval [CI] = 1.8-8.5; adjusted OR [aOR] = 4.5, 95% CI = 2.0-9.9) was detected in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset as compared to nonvaccinated individuals. Using test-negative controls, in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset, a nonsignificantly increased OR of narcolepsy was detected when compared to nonvaccinated individuals (whole study population, BC levels 1-4a: cOR = 1.9, 95% CI = 0.5-6.9; aOR = 1.8, 95% CI = 0.3-10.1). CONCLUSIONS: The findings of this study support an increased risk for narcolepsy after immunization with pandemic influenza A/H1N1/v vaccine.
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Narcolepsia/epidemiología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Alemania/epidemiología , Humanos , Control de Infecciones , Infecciones/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Vacunación/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: No comparative review of Vaccine Adverse Event Reporting System (VAERS) submissions following pandemic influenza A (H1N1) 2009 and seasonal influenza vaccinations during the pandemic season among U.S. military personnel has been published. METHODS: We compared military vs. civilian adverse event reporting rates. Adverse events (AEs) following vaccination were identified from VAERS for adults aged 17-44years after pandemic (monovalent influenza [MIV], and seasonal (trivalent inactivated influenza [IIV3], live attenuated influenza [LAIV3]) vaccines. Military vaccination coverage was provided by the Department of Defense's Defense Medical Surveillance System. Civilian vaccination coverage was estimated using data from the National 2009 H1N1 Flu Survey and the Behavioral Risk Factor Surveillance System survey. RESULTS: Vaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain-Barré Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million). CONCLUSIONS: Despite higher vaccination coverage in service personnel, the rate of serious AEs following MIV was about half that in civilians. The rate of GBS reported following MIV was higher in the military.
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Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Vacunación/efectos adversos , Adolescente , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Femenino , Síndrome de Guillain-Barré/inducido químicamente , Humanos , Subtipo H1N1 del Virus de la Influenza A , Masculino , Personal Militar , Estudios Retrospectivos , Estados Unidos , Vacunación/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND: The healthcare and socio-economic burden resulting from influenza A (H1N1) pdm09 in Spain was considerable. Our aim was to estimate and compare the management (resource utilization) and economic healthcare impact in an at-risk group of unvaccinated pregnant women with an unvaccinated group of non-pregnant woman of childbearing age (15-44 yr old). METHODS: We addressed this question with a longitudinal, observational, multicentre study. Inputs were the requirements in managing both groups of women. Outcome measures were healthcare costs. Direct healthcare (including medical utilisation, prescriptions of antivirals, medication, diagnostic tests, and hospitalisation) costs and indirect (productivity loss) costs were considered. Unit of cost was attributed to the frequency of health service resources utilisation. The mean cost per patient was calculated in this group of women. RESULTS: We found that the influenza clinical pattern was worse in non-pregnant women as they had a high medical risk of 20.4% versus 6.1% of pregnant women. Non-pregnant required more antipyretics and antibiotics, and needed more health service resource utilisation (338 medical visits in non-pregnant women vs. 42 in pregnant women). The total cost of non-pregnant women was higher (4,689.4/non-pregnant and 2,945.07/pregnant). CONCLUSIONS: Cost per (H1N1) pdm09 was lower for pregnant women, probably due to more preventive measures adopted for their protection in Spain. The highest costs were incurred by hospitalisations/day and work absenteeism for non-pregnant than for pregnant women. These data will allow better future pandemic influenza planning.
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Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.
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Apoptosis , Coinfección/fisiopatología , Infecciones por VIH/fisiopatología , VIH-1/fisiología , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/fisiopatología , Células Jurkat/citología , Animales , Línea Celular , Embrión de Pollo , Coinfección/genética , Coinfección/metabolismo , Coinfección/virología , Salud Global , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , VIH-1/genética , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/genética , Gripe Humana/metabolismo , Gripe Humana/virología , Células Jurkat/metabolismo , Células Jurkat/virología , FN-kappa B/genética , FN-kappa B/metabolismo , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismoRESUMEN
The exact molecular pathways involved in the pathogenesis of influenza are yet unclear. In the present study we investigated the upper respiratory proteome in influenza patients. 200 nasal and throat swab samples were collected from patients suffering from acute respiratory illness. These samples were confirmed for influenza pandemic A/H1N1/2009 and influenza type B using qRT-PCR. 10 similar swabs were collected from healthy individuals and were used as controls. Proteins were extracted from the cell pellets and were subjected to 2-D gel electrophoresis. The differentially expressed proteins were identified using MALDI-TOF. Identified proteins were classified into different functional groups based on functions reported in the databases. 25 % of these proteins were involved in cytoskeletal formation, whereas 14 % were involved in signal transduction. Proteins involved in anti-viral responses, Ca-signaling, transport, and tumor suppression constituted 10 % each, where as 5 % of proteins each belong to Nicotinic acetylcholine receptor, Protein Synthesis and anti-bacterial proteins. 10 % of the proteins have not been described previously. This is the first report on respiratory proteome profile in Influenza patients. The study emphasizes the role of such profiling studies using multiple platforms for bio-marker discoveries, especially non-invasive diagnostic marker in Influenza and other infectious diseases.
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Large cohort studies demonstrated the safety of vaccination with the AS03 adjuvanted pandemic influenza vaccine, but data on first trimester vaccination safety are limited. We conducted a nationwide register-based retrospective cohort study in Finland, included singleton pregnancies present on 01 November 2009 and followed them from 01 November 2009 until delivery. Pregnancies with abortive outcome, pregnancies that started before 01 February 2009 and pregnancies of women, who received the AS03 adjuvanted pandemic influenza vaccine prior to the onset of pregnancy, were excluded. Our main outcome measures were hazard ratios comparing the risk of stillbirth, early neonatal death, moderately preterm birth, very preterm birth, moderately low birth weight, very low birth weight, and being small for gestational age between pregnancies exposed and unexposed to maternal influenza A(H1N1)pdm09 vaccination. The study population comprised 43,604 pregnancies; 34,241 (78.5%) women were vaccinated at some stage during pregnancy. The rates of stillbirth, early neonatal death, moderately preterm birth, and moderately low birth weight were similar between pregnant women exposed and unexposed to influenza A(H1N1)pdm09 vaccination. After adjusting for known risk factors, the relative rates were 0.90 (95% confidence interval 0.55-1.45) for very preterm birth, 0.84 (0.61-1.16) for very low birth weight, and 1.17 (0.98-1.40) for being small for gestational age. Also, in the subanalysis of 7839 women vaccinated during the first trimester, the rates did not indicate that maternal vaccination during the first trimester had any adverse impact on perinatal survival and health. The risk of adverse pregnancy outcomes was not associated with the exposure to the AS03 adjuvanted pandemic influenza vaccine. This study adds reassuring evidence on the safety of AS03 adjuvanted influenza vaccines when given in the first trimester and supports the recommendation of influenza vaccination to all pregnant women through all stages of pregnancy.
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Esquemas de Inmunización , Salud del Lactante , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/efectos adversos , Polisorbatos/efectos adversos , Complicaciones del Embarazo/epidemiología , Escualeno/efectos adversos , alfa-Tocoferol/efectos adversos , Adolescente , Adulto , Combinación de Medicamentos , Femenino , Finlandia , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Vacunas contra la Influenza/administración & dosificación , Polisorbatos/administración & dosificación , Embarazo , Complicaciones del Embarazo/inducido químicamente , Nacimiento Prematuro/epidemiología , Estudios Retrospectivos , Escualeno/administración & dosificación , Mortinato/epidemiología , Análisis de Supervivencia , Adulto Joven , alfa-Tocoferol/administración & dosificaciónRESUMEN
BACKGROUND: Overproduction of pro-inflammatory cytokines and chemokines is frequently associated with severe clinical manifestations in patients infected with influenza A/H1N1 virus. Micro-RNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression and are potential biomarkers and therapeutic targets in different inflammatory conditions. METHODS: We studied the circulating and miRNA profiles in critically ill A/H1N1 patients, A/H1N1 patients with milder disease, asymptomatic housemates and healthy controls. Cytokine, chemokine and growth factors that were potential targets of differentially expressed miRNAs were assessed. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and interactome analysis of these miRNAs were also performed. RESULTS: Critically ill patients exhibited a significant over-expression of circulating miR-150 (p<0.005) when compared to patients with milder disease. miR-29c, miR-145 and miR-22 were differentially expressed in patients with severe A/H1N1 disease whereas miR-210, miR-126 and miR-222 were downregulated in individuals exposed to the A/H1N1 virus. Significant correlations (p<0.05) between circulating levels of miR-150 with IL-1ra, IL-2, IL-6, CXCL8, IFN-γ, CXCL10 and G-CSF were detected, particularly in critically ill patients. CONCLUSION: The up-regulation of miR-150 is associated with poorer outcomes of A/H1N1 infection. The differential expression of miRNAs related with immune processes in severe A/H1N1 disease supports the potential role of these miRNAs as biomarkers of disease progression.
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Biomarcadores/sangre , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/genética , MicroARNs/genética , Índice de Severidad de la Enfermedad , Adulto , Estudios de Casos y Controles , Células Cultivadas , Citocinas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Perfilación de la Expresión Génica , Humanos , Gripe Humana/sangre , Gripe Humana/virología , Masculino , MicroARNs/sangre , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVES: The aim of this study is to describe demographic, clinical and epidemiological characteristics of cases with laboratory-confirmed pandemic influenza virus A(H1N1)pdm09 reported in Slovakia from May 28, 2009 to December 30, 2009 and analyse the association between risk factors and severe outcome of these cases. BACKGROUND: In the spring of 2009, an outbreak of a pandemic influenza virus A(H1N1)pdm09, emerged in Mexico and spread globally. Until December 2009, 1,014 cases were notified in Slovakia. METHODS: The data were collected within national influenza surveillance system. Odds ratios (95% CI) were calculated. Associations were found to be significantly associated with the worse outcome (p < 0.05) in the univariate analysis and were adjusted for possible effects of age and sex by using a logistic regression model. RESULTS: Out of the total number of 1,014 cases, 131 (12.9 %) cases were hospitalized, and 43 (4.2 %) of those were admitted to intensive care units. During the reporting period, 38 deaths were reported, representing a case fatality rate of 3.75 %. The median age of severe cases (35 years, IQR = 29 y) was significantly higher than the median age of mild cases (24 years, IQR = 19 y; p < 0.001). By using a logistic regression, we found out that chronic obstructive pulmonary disease (COPD) (aOR = 9.2; 95%CI: 1.42-59.98), cardiovascular diseases (aOR = 14.97; 95%CI: 5.49-40.79), malignity (aOR = 7.6; 95%CI: 1.95-29.37) and gravidity (aOR = 55.21; 95% CI: 14.40-211.58) were significantly associated with severe outcomes of the cases. CONCLUSION: The fact, that 35% of severely ill patients did not report any risk factor suggests the importance of vaccination as a prevention of influenza (Tab. 2, Fig. 1, Ref. 18). Text in PDF www.elis.sk.
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Hospitalización/estadística & datos numéricos , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/epidemiología , Unidades de Cuidados Intensivos/estadística & datos numéricos , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/epidemiología , Niño , Preescolar , Comorbilidad , Brotes de Enfermedades , Femenino , Humanos , Lactante , Gripe Humana/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neoplasias/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Eslovaquia/epidemiología , Adulto JovenRESUMEN
Clinical trials have shown that AS03-adjuvanted H5N1 and A(H1N1)pdm09 vaccines are highly immunogenic, although with an increased reactogenicity profile relative to non-adjuvanted vaccines in terms of the incidence of common injection site and systemic adverse events (AEs). We evaluated pooled safety data from 22,521 adults who had received an AS03-adjuvanted H5N1 or A(H1N1)pdm09 influenza or control vaccine with the purpose to identify medically-attended AEs (MAEs), including subsets of serious AEs (SAEs), potentially immune-mediated diseases (pIMDs), and AEs of special interest (AESI), and to explore a potential association of these AEs with the administration of an AS03-adjuvanted influenza vaccine. For participants who had received an AS03-adjuvanted vaccine, the relative risks (RRs) for experiencing a MAE or a SAE compared to control group (participants who had received a non-adjuvanted vaccine or saline placebo) were 1.0 (95% confidence interval [CI]: 0.9; 1.1) and 1.1 (95% CI: 0.9; 1.4), respectively. The overall RRs for experiencing an AESI or a pIMD (AS03-adjuvanted vaccine/control) were 1.2 (95% CI: 0.9; 1.6) and 1.7 (95% CI: 0.8; 3.8), respectively. Thirty-8 participants in the AS03-adjuvanted vaccine group had a pIMD reported after vaccine administration, yielding an incidence rate (IR) of 351.9 (95% CI: 249.1; 483.1) per 100,000 person-years. The estimated IRs in the AS03-adjuvanted vaccine group were greater than the literature reported rates for: facial paresis/VIIth nerve paralysis, celiac disease, thrombocytopenia and ulcerative colitis. These results do not support an association between AS03-adjuvanted H5N1 and A(H1N1)pdm09 vaccines and the AEs collected in the trials included in the analysis.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/uso terapéutico , Polisorbatos/efectos adversos , Escualeno/efectos adversos , alfa-Tocoferol/efectos adversos , Adyuvantes Inmunológicos/uso terapéutico , Adolescente , Adulto , Anticuerpos Antivirales/inmunología , Combinación de Medicamentos , Femenino , Humanos , Vacunas contra la Influenza/efectos adversos , Gripe Humana/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Polisorbatos/uso terapéutico , Riesgo , Escualeno/uso terapéutico , Vacunación , Adulto Joven , alfa-Tocoferol/uso terapéuticoRESUMEN
OBJECTIVE: To test the applicability of the Theory of Planned Behavior (TPB) in college students who have not previously received the A/H1N1 vaccine. PARTICIPANTS: Undergraduate communication students at a metropolitan southern university. METHODS: In January-March 2010, students from voluntarily participating communication classes completed a hardcopy survey assessing TPB and clinically significant constructs. Hierarchical regression equations predicted variance in vaccine intentions of students who had not received a flu shot (N=198; 70% Caucasian). RESULTS: The TPB model explained 51.7% (p<.001) of variance in vaccine intentions. Controlling for side effects, self-efficacy and perceived comparative susceptibility predicted intentions when entered in the first block, whereas attitudes, subjective norms, and perceived behavioral control significantly contribute when entered in the second block. CONCLUSIONS: For students who have not previously received a flu vaccine, vaccine communication should utilize self-efficacy and perceived comparative susceptibility to employ the TPB to promote vaccine intentions.
Asunto(s)
Conducta , Conocimientos, Actitudes y Práctica en Salud , Subtipo H1N1 del Virus de la Influenza A , Estudiantes/psicología , Universidades , Vacunación/psicología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
In this study, recombinant hemagglutinin protein (rH1N1HA) of Pandemic influenza virus and polyclonal antibodies against it for biosensor applications have been characterized. For rapid and high sensitive detection of H1N1 virus or its antibodies, PCR-free and label free detection method based on a surface plasmon resonance technique has been proposed. The glycosylated H1N1HA protein was expressed in yeast and the authenticity of the expressed protein was confirmed by Western blotting. Rabbit polyclonal antibodies developed against rH1N1HA protein were evaluated for their ability to neutralize H1N1 virus through plaque reduction neutralization test and indirect ELISA. Affinity purified anti-H1N1HA IgG were characterized further for their specificity, affinity of interaction, the association and dissociation rates at which they interact through surface plasmon resonance technique. The equilibrium constant and maximum binding capacity of analyte was found to be 49.7 nM and 47.28m°, respectively. The assay could detect a lowest IgG of 0.5 ng on a rH1N1HA coated chip. Combined with the high sensitivity of surface plasmon resonance technique and specificity of the reagents, it is possible to develop a rapid detection assay for monitoring influenza infections.
Asunto(s)
Anticuerpos Antivirales/metabolismo , Antígenos Virales/metabolismo , Técnicas Biosensibles/métodos , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Animales , Anticuerpos Antivirales/aislamiento & purificación , Antígenos Virales/aislamiento & purificación , Glicoproteínas Hemaglutininas del Virus de la Influenza/aislamiento & purificación , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Masculino , Unión Proteica , Conejos , Proteínas Recombinantes/aislamiento & purificación , Proteínas Recombinantes/metabolismo , Sensibilidad y Especificidad , Resonancia por Plasmón de SuperficieRESUMEN
It is not well-known whether apoptosis signaling affects influenza virus infection and reproduction in human lung epithelial cells. Using A549 cell line, we studied the relationship of some apoptosis-associated molecules with novel pandemic influenza A (H1N1) virus, A/California/04/2009. Infected cells displayed upregulated Fas ligand, activated FADD and caspase-8, and downregulated FLIP in the extrinsic apoptotic pathway. p53 expression increased and Bcl-XL expression decreased in the intrinsic pathway. Expression of pre-apoptotic molecules (FasL, FADD, and p53) increased virus replication, while inhibition of activity of FADD, caspase-8 and caspase-3, and expression of anti-apoptotic proteins (FLIP and Bcl-XL) decreased virus replication. p38, ERK and JNK from MAPK pathways were activated in infected cells, and inhibition with their inhibitors diminished virus replication. In the p38 superfamily, p38α expression increased viral RNA production, while expression of p38ß and p38γ decreased. These data indicated that influenza virus induces apoptotic signaling pathways, which benefit virus replication.
Asunto(s)
Apoptosis/inmunología , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Humana/inmunología , Gripe Humana/virología , Replicación Viral/inmunología , Caspasas/metabolismo , Línea Celular Tumoral , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/metabolismo , Humanos , Gripe Humana/metabolismo , Sistema de Señalización de MAP Quinasas/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The pandemic influenza A/H1N1 outbreak resulted in 18,449 deaths in over 214 countries. In Taiwan, the influenza rapid test, an in vitro diagnostic device (Flu-IVD), only requires documented reviews for market approval by the Taiwan Food and Drug Administration. The purpose of this study was to investigate the analytical sensitivity and specificity of Flu-IVDs used in Taiwan. Analytical sensitivity and specificity tests were performed for influenza antigens A/California/7/2009 (H1N1) virus, A/Victoria/210/2009 (H3N2) virus, B/ Brisbane/60/08 virus, and human coronavirus OC43. A total of seven domestic and 31 imported Flu-IVD samples were collected, of which, 20 samples had inadequate labeling, including those with removed package inserts or incorrect insert information. The analytical sensitivity of Flu-IVDs for A/H1N1, A/H3N2, and Flu B was 500-1000 ng/mL, 1000 ng/mL, and 1000 ng/mL, respectively. For the 50% cell culture infective dose (CCID50) label, the average A/H1N1 and A/H3N2 sensitivity for Flu-IVDs was log10 5.8 ± 0.5 and log10 6.6 ± 0.5 CCID50/mL, respectively. As to the specificity test, no product cross-reacted with human coronavirus OC43. This study provides important information on the Flu-IVD regulation status and can thus help the government formulate policies for the regulation of in vitro diagnostic devices in Taiwan.