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2.
Medicine (Baltimore) ; 99(2): e18504, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914021

RESUMEN

We aimed to evaluate the clinical significance of bacterial coexistence and the coinfection dynamics between bacteria and respiratory viruses among young children. We retrospectively analyzed clinical data from children aged < 5 years hospitalized with a community-acquired single respiratory viral infection of influenza, adenovirus, or RSV during 2 recent consecutive influenza seasons. Remnant respiratory specimens were used for bacterial PCR targeting Moraxella catarrhalis, Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus.A total of 102 children were included; median age was 0.8 years and 44.1% had underlying comorbidities. Overall, 6.8% (7/102) of cases were classified as severe diseases requiring intensive care unit admission and/or mechanical ventilation and ranged from 8.8% for a patient with RSV and 7.6% for those with adenovirus to 0% for those with influenza viruses. The overall viral-bacterial codetection rate was 59.8% (61/102); M catarrhalis was the most frequent (33.3%), followed by H influenzae (31.4%). Influenza cases showed higher bacterial codetection rates (80.0%; 8/10) compared with those with adenoviruses (69.2%; 9/13) and RSV (55.7%; 44/79). S pneumoniae and H influenzae codetections were associated with reduced severity (aOR, 0.24; 95% CI, 0.07-0.89), and reduced risk of wheezing (aOR, 0.36; 95% CI, 0.13-0.98), respectively.We observed the interactions between respiratory viruses and bacteria and the clinical significance of viral-bacterial coexistence in upper airway on disease severity. Future study will be necessary to elucidate the active interactions between different viruses and bacteria and give clues to risk stratified strategy in the management of respiratory infections among young children.


Asunto(s)
Adenoviridae/aislamiento & purificación , Haemophilus influenzae/aislamiento & purificación , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , Infecciones por Adenoviridae/diagnóstico , Infecciones por Adenoviridae/virología , Bacterias/genética , Preescolar , Coinfección/microbiología , Coinfección/virología , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/virología , Femenino , Hospitalización , Humanos , Lactante , Recién Nacido , Gripe Humana/diagnóstico , Gripe Humana/virología , Masculino , Prevalencia , Ruidos Respiratorios/diagnóstico , Ruidos Respiratorios/etiología , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/genética , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Staphylococcus aureus/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Virus/genética
3.
MMWR Morb Mortal Wkly Rep ; 69(2): 40-43, 2020 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-31945035

RESUMEN

Multiple genetically distinct influenza B/Victoria lineage viruses have cocirculated in the United States recently, circulating sporadically during the 2018-19 season and more frequently early during the 2019-20 season (1). The beginning of the 2019-20 influenza season in Louisiana was unusually early and intense, with infections primarily caused by influenza B/Victoria lineage viruses. One large pediatric health care facility in New Orleans (facility A) reported 1,268 laboratory-confirmed influenza B virus infections, including 23 hospitalizations from July 31 to November 21, 2019, a time when influenza activity is typically low. During this period, Louisiana also reported one pediatric death associated with influenza B virus infection. An investigation of the influenza B virus infections in Louisiana, including medical and vaccine record abstraction on 198 patients, primarily from facility A, with sporadic cases from other facilities in the state, found that none of the patients had received 2019-20 seasonal influenza vaccine, in part because influenza activity began before influenza vaccination typically occurs. Among 83 influenza B viruses sequenced from 198 patients in Louisiana, 81 (98%) belonged to the recently emerged B/Victoria V1A.3 genetic subclade. Nationally, to date, B/Victoria viruses are the most commonly reported influenza viruses among persons aged <25 years (2). Of the 198 patients in the investigation, 95% were aged <18 years. Although most illnesses were uncomplicated, the number of hospitalizations, clinical complications, and the reported pediatric death in Louisiana serve as a reminder that, even though influenza B viruses are less common than influenza A viruses in most seasons, influenza B virus infection can be severe in children. All persons aged ≥6 months should receive an annual influenza vaccination if they have not already received it (3). Antiviral treatment of influenza is recommended as soon as possible for all hospitalized patients and for outpatients at high risk for influenza complications (including children aged <2 years and persons with underlying medical conditions) (4).


Asunto(s)
Virus de la Influenza B/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Adolescente , Adulto , Niño , Preescolar , Humanos , Lactante , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Louisiana/epidemiología , Estaciones del Año , Adulto Joven
4.
BMC Infect Dis ; 19(1): 1012, 2019 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-31783806

RESUMEN

BACKGROUND: Influenza is the most frequent cause of acute upper respiratory tract infections during winter season. Although rare, neurological manifestations are known to occur during influenza infection and approximatively three-quarters of cases are in children. In this study, we aimed to characterize the burden and clinical spectrum of influenza-associated encephalopathy and encephalitis in children admitted at a tertiary pediatric hospital in Italy over two influenza seasons (2017-2019). METHODS: We retrospectively analyzed clinical, laboratory, instrumental data and outcome of patients discharged with ICD9-CM 487.0 code. RESULTS: Fifteen children (13.1% of those discharged with a diagnosis of influenza infection in the study period), had influenza-associated central nervous system (CNS) manifestations. Eight patients (53.3%) were diagnosed as influenza encephalitis, 7 (46.7%) as influenza encephalopathy. Median age was 27 months. In children under 2 years of age (40% of all cases) altered consciousness was the most frequent neurological manifestation while respiratory symptoms were present at admission in all cases. Younger children also required intensive care support more frequently. Five subjects (33.3%) presented comorbidity. None of the patients had received seasonal influenza vaccination. The median time from onset of respiratory signs to onset of neurological manifestations was 24 h. Cerebrospinal fluid (CSF) analysis was normal in most patients and polymerase chain reaction for influenza virus RNA on CSF, when performed, was negative in all samples. Neuroradiological investigations, performed in 5 children, reported cortical and subcortical white matter signal alterations. Oseltamivir was administered only in 2 cases. Fourteen patients recovered without sequelae, and only a 2-year-old girl had minimal impairment in fine motor skills at discharge. CONCLUSIONS: All children presenting acute neurological features during influenza season should be evaluated for influenza-associated CNS complications even if the respiratory involvement is mild. Absence of underlying diseases or other risk factors are not protective factors against CNS influenza-associated complications. The lack of CSF pleocytosis does not exclude CNS involvement. Children under 2 years of age are at higher risk of requiring intensive care support.


Asunto(s)
Encefalitis/diagnóstico , Gripe Humana/patología , Niño , Preescolar , Encefalitis/etiología , Femenino , Hospitales Pediátricos , Humanos , Lactante , Gripe Humana/complicaciones , Gripe Humana/virología , Italia , Masculino , Orthomyxoviridae/genética , Orthomyxoviridae/aislamiento & purificación , ARN Viral/líquido cefalorraquídeo , Estudios Retrospectivos , Estaciones del Año , Centros de Atención Terciaria
5.
BMC Infect Dis ; 19(1): 990, 2019 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-31752738

RESUMEN

BACKGROUND: Since 1985, two antigenically distinct lineages of influenza B viruses (Victoria-like and Yamagata-like) have circulated globally. Trivalent seasonal influenza vaccines contain two circulating influenza A strains but a single B strain and thus provide limited immunity against circulating B strains of the lineage not included in the vaccine. In this study, we describe the characteristics of influenza B viruses that caused respiratory illness in the population in Italy over 13 consecutive seasons of virological surveillance, and the match between the predominant influenza B lineage and the vaccine B lineage, in each season. METHODS: From 2004 to 2017, 26,886 laboratory-confirmed influenza cases were registered in Italy, of which 18.7% were type B. Among them, the lineage of 2465 strains (49%) was retrieved or characterized in this study by a real-time RT-PCR assay and/or sequencing of the hemagglutinin (HA) gene. RESULTS: Co-circulation of both B lineages was observed each season, although in different proportions every year. Overall, viruses of B/Victoria and B/Yamagata lineages caused 53.3 and 46.7% of influenza B infections, respectively. A higher proportion of infections with both lineages was detected in children, and there was a declining frequency of B/Victoria detections with age. A mismatch between the vaccine and the predominant influenza B lineage occurred in eight out of thirteen influenza seasons under study. Considering the seasons when B accounted for > 20% of all laboratory-confirmed influenza cases, a mismatch was observed in four out of six seasons. Phylogenetic analysis of the HA1 domain confirmed the co-circulation of both lineages and revealed a mixed circulation of distinct evolutionary viral variants, with different levels of match to the vaccine strains. CONCLUSIONS: This study contributes to the understanding of the circulation of influenza B viruses in Italy. We found a continuous co-circulation of both B lineages in the period 2004-2017, and determined that children were particularly vulnerable to Victoria-lineage influenza B virus infections. An influenza B lineage mismatch with the trivalent vaccine occurred in about two-thirds of cases.


Asunto(s)
Virus de la Influenza B/aislamiento & purificación , Gripe Humana/virología , Monitoreo Epidemiológico , Humanos , Virus de la Influenza B/clasificación , Virus de la Influenza B/genética , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Italia/epidemiología , Filogenia , Estudios Retrospectivos , Estaciones del Año
6.
BMC Infect Dis ; 19(1): 964, 2019 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-31718571

RESUMEN

BACKGROUND: The aim of this study was to evaluate the correlation between clinical and imaging findings with a worse clinical outcome in patients with a confirmed diagnosis of H1N1 influenza A virus. METHODS: Patients with a positive viral test for influenza A H1N1 in 2016 and chest radiography (CR) and/or computed tomography (CT) results had clinical and imaging data reviewed. Hospitalization, admission to the intensive care unit or death were defined as worse clinical outcomes. The association between clinical and imaging features and the worse outcome was calculated in a logistical regression model. RESULTS: Eighty of 160 (50%) patients were men, with a mean age of 43 ± 19 years. The most common symptoms were as follows: flu-like symptoms 141/160 (88%), dyspnea (25/160, 17%), and thoracic pain (7/160, 5%). Abnormalities on CR were detected in 8/110 (7%) patients, and 43/59 (73%) patients had an abnormal CT. The following variables were associated with worse clinical outcomes: the presence of diabetes mellitus (DM), hypertension, dyspnea, thoracic pain, abnormal CR or CT regardless of the type of finding, CT with consolidation or ground glass opacity. CONCLUSIONS: The presence of DM, hypertension, dyspnea, thoracic pain, or an abnormal CR or CT on admission were associated with worse clinical outcomes in patients with H1N1 influenza A virus infection. Thus, the use of readily accessible clinical and imaging features on admission may have a role in the evaluation of patients with H1N1 infection.


Asunto(s)
Gripe Humana/diagnóstico , Adulto , Femenino , Hospitalización , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/patología , Gripe Humana/virología , Unidades de Cuidados Intensivos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tórax/diagnóstico por imagen , Tomografía Computarizada por Rayos X
7.
Artículo en Inglés | MEDLINE | ID: mdl-31738866

RESUMEN

The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2018 influenza season. In this observational surveillance system, cases were defined as patients admitted to any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data were also collected on a frequency-matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 3 April to 31 October 2018 (the 2018 influenza season), 769 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 30% were elderly (≥65 years), 28% were children (<16 years), 6.4% were Aboriginal and Torres Strait Islander peoples, 2.2% were pregnant and 66% had chronic comorbidities. A small proportion of FluCAN admissions were due to influenza B (13%). Estimated vaccine coverage was 77% in the elderly (≥65 years), 45% in non-elderly adults with medical comorbidities and 26% in children (<16 years) with medical comorbidities. The estimated vaccine effectiveness (VE) in the target population was 52% (95% CI: 37%, 63%). There were a smaller number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2018 than in 2017, with the demographic profile reflecting the change in circulating subtype from A/H3N2 to A/H1N1.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Cobertura de Vacunación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Informes Anuales como Asunto , Australia/epidemiología , Estudios de Casos y Controles , Femenino , Hospitalización , Hospitales , Humanos , Gripe Humana/prevención & control , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Embarazo , Vigilancia de Guardia , Adulto Joven
8.
Artículo en Inglés | MEDLINE | ID: mdl-31738867

RESUMEN

Introduction: Maternal influenza vaccination was introduced in 2010 due to the high morbidity and mortality associated with influenza in pregnancy. The aim of this study was to assess the maternal influenza vaccination uptake in Northern Territory public hospitals and identify gaps to improve uptake. Methods: Birth data from Northern Territory (NT) public hospitals obtained from the Perinatal Register for deliveries in 2016 were merged with vaccination records from the NT immunisation register. Results: There were 3,392 viable pregnancies in NT public hospitals in 2016 with 45.6% vaccination coverage against influenza. There was a statistically significant difference in coverage with 68.5% in Indigenous vs 31.7% in non-Indigenous deliveries (p < 0.001), yielding an odds ratio of 4.67 (95% CI 4.02, 5.42) for maternal influenza vaccination across Indigenous status. Influenza vaccination coverage for preterm births (< 37 weeks) was low especially in non-Indigenous mothers at 27.2% vs 65.05% in Indigenous mothers (p < 0.001). A distinct immunisation administration pattern was noted for 2016 with 58.9% of vaccinations occurring between April and June regardless of Indigenous status and maternal gestational age. This correlated with the annual influenza immunisation campaign by the NT and Commonwealth. Conclusion: A year-round maternal influenza vaccination campaign is crucial to avoid missed opportunities and increase vaccination protection for mother and baby. Antenatal influenza vaccination campaign with health care workers education and increasing patient awareness should continue throughout the year.


Asunto(s)
Programas de Inmunización , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Cobertura de Vacunación , Vacunación , Adolescente , Adulto , Femenino , Humanos , Gripe Humana/virología , Persona de Mediana Edad , Madres , Northern Territory , Grupo de Ascendencia Oceánica , Embarazo , Sistema de Registros , Estudios Retrospectivos , Adulto Joven
9.
Emerg Microbes Infect ; 8(1): 1535-1545, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31661383

RESUMEN

Influenza A virus infections occur in different species, causing mild to severe respiratory symptoms that lead to a heavy disease burden. Eurasian avian-like swine influenza A(H1N1) viruses (EAS-H1N1) are predominant in pigs and occasionally infect humans. An influenza A(H1N1) virus was isolated from a boy who was suffering from fever and headache and designated as A/Tianjin-baodi/1606/2018(H1N1). Full-genome sequencing and phylogenetic analysis revealed that A/Tianjin-baodi/1606/2018(H1N1) is a novel reassortant EAS-H1N1 containing gene segments from EAS-H1N1 (HA and NA), classical swine H1N1(NS) and A(H1N1)pdm09(PB2, PB2, PA, NP and M) viruses. The isolation and analysis of A/Tianjin-baodi/1606/2018(H1) provide further evidence that EAS-H1N1 poses a threat to human health and greater attention should be paid to surveillance of influenza virus infection in pigs and humans.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/virología , Infecciones por Orthomyxoviridae/veterinaria , Virus Reordenados/aislamiento & purificación , Enfermedades de los Porcinos/virología , Animales , Niño , China , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Aviar/virología , Masculino , Infecciones por Orthomyxoviridae/virología , Filogenia , Aves de Corral , Enfermedades de las Aves de Corral/virología , Virus Reordenados/clasificación , Virus Reordenados/genética , Porcinos
10.
MMWR Morb Mortal Wkly Rep ; 68(40): 880-884, 2019 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-31600182

RESUMEN

During May 19-September 28, 2019,* low levels of influenza activity were reported in the United States, with cocirculation of influenza A and influenza B viruses. In the Southern Hemisphere seasonal influenza viruses circulated widely, with influenza A(H3) predominating in many regions; however, influenza A(H1N1)pdm09 and influenza B viruses were predominant in some countries. In late September, the World Health Organization (WHO) recommended components for the 2020 Southern Hemisphere influenza vaccine and included an update to the A(H3N2) and B/Victoria-lineage components. Annual influenza vaccination is the best means for preventing influenza illness and its complications, and vaccination before influenza activity increases is optimal. Health care providers should recommend vaccination for all persons aged ≥6 months who do not have contraindications to vaccination (1).


Asunto(s)
Salud Global/estadística & datos numéricos , Vacunas contra la Influenza/química , Gripe Humana/epidemiología , Vigilancia de la Población , Farmacorresistencia Viral , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/efectos de los fármacos , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/efectos de los fármacos , Virus de la Influenza B/genética , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/virología , Estaciones del Año , Estados Unidos/epidemiología
11.
BMC Infect Dis ; 19(1): 858, 2019 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-31619209

RESUMEN

BACKGROUND: Intravenous (IV) zanamivir could be a suitable alternative for the treatment of severe influenza A(H1N1)pdm09 infection in patients who are unable to take oral or inhaled medication, for example, those on mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, data on the clinical outcomes of such patients is limited. CASE PRESENTATION: We report the clinical outcomes of four patients who were admitted at the intensive care unit during the 2017-2018 influenza season with severe sepsis (SOFA score > 11) and acute respiratory distress syndrome requiring ECMO and mechanical ventilation. Two patients were immune-compromised. The A(H1N1)pdm09 genome was confirmed by polymerase chain reaction (PCR) on nasopharyngeal specimen swabs prior to administration of IV zanamivir at a dose of 600 mg twice daily. Weekly qualitative PCR analysis was done to monitor viral clearance, with zanamivir treatment being discontinued upon receipt of negative results. In addition, the patients were managed for concomitant multidrug-resistant bacterial infections, with infection resolution confirmed with blood cultures. The median time for zanamivir treatment was 10 days (IQR 10-17). The clinical outcome was favourable with all four patients surviving and improving clinically. All four patients achieved viral clearance of A(H1N1)pdm09 genome, and resolution of multidrug-resistant bacterial infections. CONCLUSIONS: IV zanamivir could be a good therapeutic option in patients with severe influenza A(H1N1)pdm09 infection who are unable to take oral or aerosolised antiviral medication. We recommend prospective randomized control trials to support this hypothesis.


Asunto(s)
Antivirales/uso terapéutico , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/tratamiento farmacológico , Zanamivir/uso terapéutico , Humanos , Gripe Humana/fisiopatología , Gripe Humana/virología
12.
Emerg Microbes Infect ; 8(1): 1465-1478, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31608791

RESUMEN

The ANP32A is responsible for mammalian-restricted influenza virus polymerase activity. However, the mechanism of ANP32A modulation of polymerase activity remains poorly understood. Here, we report that chicken ANP32A (chANP32A) -X1 and -X2 stimulated mammalian-restricted PB2 627E polymerase activity in a dose-dependent manner. Distinct effects of ANP32A constructs suggested that the 180VK181 residues within chANP32A-X1 are necessary but not sufficient to stimulate PB2 627E polymerase activity. The PB2 N567D, T598V, A613V or F636L mutations promoted PB2 627E polymerase activity and chANP32A-X1 showed additive effects, providing further support that species-specific regulation of ANP32A might be only relevant with the PB2 E627K mutation. Rescue of cycloheximide-mediated inhibition showed that ANP32A is species-specific for modulation of vRNA but not mRNA and cRNA, demonstrating chANP32A-X1 compensated for defective cRNPs produced by PB2 627E virus in mammalian cells. The promoter mutations of cRNA enhanced the restriction of PB2 627E polymerase in mammalian cells, which could be restored by chANP32A-X1, indicating that ANP32A is likely to regulate the interaction of viral polymerase with RNA promoter. Coimmunoprecipitation showed that ANP32A did not affect the primary cRNPs assembly. We propose a model that chANP32A-X1 regulates PB2 627E polymerase for suitable interaction with cRNA promoter for vRNA replication.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/enzimología , Subtipo H7N9 del Virus de la Influenza A/enzimología , Subtipo H9N2 del Virus de la Influenza A/enzimología , Gripe Aviar/metabolismo , Gripe Humana/metabolismo , Enfermedades de las Aves de Corral/metabolismo , ARN Replicasa/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas Virales/metabolismo , Secuencia de Aminoácidos , Animales , Pollos , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/fisiología , Subtipo H7N9 del Virus de la Influenza A/genética , Subtipo H7N9 del Virus de la Influenza A/fisiología , Subtipo H9N2 del Virus de la Influenza A/genética , Subtipo H9N2 del Virus de la Influenza A/fisiología , Gripe Aviar/genética , Gripe Aviar/virología , Gripe Humana/genética , Gripe Humana/virología , Mutación , Enfermedades de las Aves de Corral/genética , Enfermedades de las Aves de Corral/virología , Unión Proteica , ARN Replicasa/genética , ARN Viral/genética , ARN Viral/metabolismo , Proteínas de Unión al ARN/química , Proteínas de Unión al ARN/genética , Alineación de Secuencia , Especificidad de la Especie , Proteínas Virales/genética , Replicación Viral
13.
Int J Nanomedicine ; 14: 7533-7548, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31571862

RESUMEN

Background: The influenza A virus (IAV) is known for its high variability and poses a huge threat to the health of humans and animals. Pigs play a central role in the cross-species reassortment of IAV. Ectodomain of matrix protein 2 (M2e) is the most conserved protective antigen in IAV and can be used to develop nanovaccines through nanoparticles displaying to increase its immunogenicity. However, the high immunogenicity of nanoparticles can cause the risk of off-target immune response, and excess unwanted antibodies may interfere with the protective efficacy of M2e-specific antibodies. Therefore, it is necessary to select reasonable nanoparticles to make full use of antibodies against nanoparticles while increasing the level of M2e-specific antibodies. Porcine circovirus type 2 (PCV2) is the most susceptible virus in pigs and can promote IAV infection. It is meaningful to develop a vaccine that can simultaneously control swine influenza virus (SIV) and PCV2. Methods: In the present study, M2e of different copy numbers were inserted into the capsid (Cap) protein of PCV2 and expressed in Escherichia coli to form self-assembled chimeric virus-like particles (VLPs) nanovaccine. BALB/c mice and pigs were immunized with these nanovaccines to explore optimal anti-IAV and anti-PCV2 immunity. Results: Cap is capable of carrying at least 81 amino acid residues (three copies of M2e) at its C-terminal without impairing VLPs formation. Cap-3M2e VLPs induced the highest levels of M2e-specific immune responses, conferring protection against lethal challenge of IAVs from different species and induced specific immune responses consistent with PCV2 commercial vaccines in mice. In addition, Cap-3M2e VLPs induced high levels of M2e-specific antibodies and PCV2-specific neutralizing antibodies in pigs. Conclusion: Cap-3M2e VLP is an economical and promising bivalent nanovaccine, which provides dual protection against IAV and PCV2.


Asunto(s)
Circovirus/inmunología , Virus de la Influenza A/inmunología , Nanopartículas/uso terapéutico , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/inmunología , Formación de Anticuerpos/inmunología , Especificidad de Anticuerpos/inmunología , Aves/virología , Proteínas de la Cápside/química , Proliferación Celular , Citocinas/metabolismo , Perros , Femenino , Humanos , Inmunidad Humoral , Gripe Aviar/inmunología , Gripe Aviar/prevención & control , Gripe Aviar/virología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Gripe Humana/virología , Linfocitos/citología , Células de Riñón Canino Madin Darby , Ratones Endogámicos BALB C , Pruebas de Neutralización , Proteínas Recombinantes/aislamiento & purificación , Porcinos , Virión/inmunología , Virión/ultraestructura
14.
PLoS Pathog ; 15(9): e1008077, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31557273

RESUMEN

Influenza A virus (IAV) is a seasonal pathogen with the potential to cause devastating pandemics. IAV infects multiple epithelial cell subsets in the respiratory tract, eliciting damage to the lungs. Clearance of IAV is primarily dependent on CD8+ T cells, which must balance control of the infection with immunopathology. Using a virus expressing Cre recombinase to permanently label infected cells in a Cre-inducible reporter mouse, we previously discovered infected club cells that survive both lytic virus replication and CD8+ T cell-mediated clearance. In this study, we demonstrate that ciliated epithelial cells, type I and type II alveolar cells can also become survivor cells. Survivor cells are stable in the lung long-term and demonstrate enhanced proliferation compared to uninfected cells. When we investigated how survivor cells evade CD8+ T cell killing we observed that survivor cells upregulated the inhibitory ligand PD-L1, but survivor cells did not use PD-L1 to evade CD8+ T cell killing. Instead our data suggest that survivor cells are not inherently resistant to CD8+ T cell killing, but instead no longer present IAV antigen and cannot be detected by CD8+ T cells. Finally, we evaluate the failure of CD8+ T cells to kill these previously infected cells. This work demonstrates that additional cell types can survive IAV infection and that these cells robustly proliferate and are stable long term. By sparing previously infected cells, the adaptive immune system may be minimizing pathology associated with IAV infection.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/virología , Evasión Inmune , Gripe Humana/inmunología , Gripe Humana/virología , Inmunidad Adaptativa , Animales , Antígeno B7-H1/inmunología , Proliferación Celular , Supervivencia Celular/inmunología , Citotoxicidad Inmunológica , Humanos , Inmunidad Celular , Virus de la Influenza A/inmunología , Virus de la Influenza A/patogenicidad , Gripe Humana/patología , Pulmón/inmunología , Pulmón/patología , Pulmón/virología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Receptor de Muerte Celular Programada 1/inmunología
15.
Biochimie ; 166: 203-213, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31518617

RESUMEN

Influenza A virus (IAV) is one of the most common infectious pathogen and associated with significant morbidity and mortality. Although processing the IAV hemagglutinin (HA) envelope glycoprotein precursor is a pre-requisite for viral membrane fusion activity, viral entry and transmission, HA-processing protease is not encoded in the IAV genome and thus the cellular trypsin-type serine HA-processing proteases determine viral infectious tropism and viral pathogenicity. The initial process of IAV infection of the airway is followed by marked upregulation of ectopic trypsin in various organs and endothelial cells through the induction of various proinflammatory cytokines, and this process has been termed the "influenza virus-cytokine-trypsin" cycle. In the advanced stage of IAV infection, the cytokine storm induces disorders of glucose and lipid metabolism and the "metabolic disorders-cytokine" cycle is then linked with the "influenza virus-cytokine-trypsin" cycle, to advance the pathogenic process into energy crisis and multiple organ failure. Application of protease inhibitors and treatment of metabolic disorders that break these cycles and their interconnection is therefore a promising therapeutic approach against influenza. This review discusses IAV pathogenicity on trypsin type serine HA-processing proteases, cytokines, metabolites and therapeutic options.


Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Virus de la Influenza A , Gripe Humana , Serina Proteasas/fisiología , Internalización del Virus/efectos de los fármacos , Animales , Pollos/virología , Citocinas/metabolismo , Humanos , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/patogenicidad , Gripe Aviar/tratamiento farmacológico , Gripe Aviar/virología , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Orthomyxoviridae/efectos de los fármacos , Orthomyxoviridae/patogenicidad , Tripsina/metabolismo
16.
BMC Complement Altern Med ; 19(1): 253, 2019 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-31510997

RESUMEN

BACKGROUND: General antiviral agents such as oseltamivir are associated with certain adverse effects and the emergence of resistance. This study investigated the phytochemical properties, antiviral activities, and safety of three herbs used in traditional Korean medicine. METHODS: Extracts of three medicinal herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) were prepared using ethanol or water. The total phenolic, flavonoid, and saponin content, condensed tannin content, and reducing sugar content of the herb extracts were determined via phytochemical screening. Tandem mass analysis was performed using an ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-Q/Orbitrap instrument. Virus titrations were determined via tissue culture infective dose (TCID50) and cytotoxicity assays. Hemolysis and hepatotoxicity were measured to determine safety. RESULTS: Among the three medicinal herbs, F. suspensa showed the highest concentration of phenolic compounds, flavonoids, and saponins. The number of phytochemical compounds detected via tandem mass analysis of B. juncea, F. suspensa, and I. britannica was 5 (including sinigrin, m/z [M-H] = 358.02), 14 (including forsythoside A, m/z [M-H] = 623.19), and 18 (including chlorogenic acid, m/z [M-H] = 353.20), respectively. The antiviral effects of the B. juncea extracts (ethanol and water) and I. britannica extract (ethanol) were further investigated. The ethanol extract of B. juncea showed a 3 Log TCID50/25 µL virus titration reduction and the water extract showed a selectivity index of 13.668 against infected influenza H1N1 virus A/NWS/33. The B. juncea extracts did not show hemolysis activities and hepatotoxicity (< 20%). The ethanol extract of I. britannica showed the most effective virus titration decrease, whereas its hemolytic and hepatotoxicity values were the most significantly different compared to the control. Despite the high concentration of phytochemicals detected in F. suspensa, the extract showed approximately 1 Log TCID50/25 µL at the highest concentration. CONCLUSION: B. juncea may show antiviral effects against H1N1 in a host. In addition, B. juncea may also show decreased disadvantages compared to other antiviral agents.


Asunto(s)
Antivirales/farmacología , Forsythia/química , Inula/química , Planta de la Mostaza/química , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Antivirales/efectos adversos , Antivirales/química , Línea Celular , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/crecimiento & desarrollo , Gripe Humana/virología , Fitoquímicos/efectos adversos , Fitoquímicos/química , Extractos Vegetales/efectos adversos , Extractos Vegetales/química
17.
BMC Infect Dis ; 19(1): 825, 2019 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-31533638

RESUMEN

BACKGROUND: Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease. METHODS: The HIS (hospital information system) modified influenza surveillance system (ISS) and a newly built pneumonia surveillance system (PSS) were used to monitor the influenza viruses in Changsha City, China. The ISS was used to monitor outpatients in two sentinel hospitals and to detect mild influenza and avian influenza cases, and PSS was used to monitor inpatients in 49 hospitals and to detect severe and death influenza cases. RESULTS: From 2005 to 2016, there were 3,551,917 outpatients monitored by the ISS system, among whom 126,076 were influenza-like illness (ILI) cases, with the ILI proportion (ILI%) of 3.55%. After the HIS was used, the reported incident cases of ILI and ILI% were increased significantly. From March, 2009 to September, 2016, there were 5,491,560 inpatient cases monitored by the PSS system, among which 362,743 were pneumonia cases, with a proportion of 6.61%. Among pneumonia cases, about 10.55% (38,260/362,743) of cases were severe or death cases. The pneumonia incidence increased each year in the city. Among 15 avian influenza cases reported from January, 2005 to September, 2016, there were 26.7% (4/15) mild cases detected by the HIS-modified ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available. CONCLUSIONS: The HIS was able to improve the efficiency of the ISS for monitoring ILI and emerging avian influenza virus. However, the efficiency of the system needs to be verified in a wider area for a longer time span in China.


Asunto(s)
Gripe Humana/diagnóstico , Neumonía/diagnóstico , Vigilancia en Salud Pública/métodos , China/epidemiología , Hospitales , Humanos , Incidencia , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H7N9 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Gripe Humana/virología , Neumonía/epidemiología , Gestión de Riesgos
18.
Artículo en Inglés | MEDLINE | ID: mdl-31522661

RESUMEN

The Influenza Complications Alert Network (FluCAN) is a sentinel-hospital-based surveillance program that operates at sites in all jurisdictions in Australia. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2017 influenza season. In this observational surveillance system, cases were defined as patients admitted to any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data are also collected on a frequency-matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 3 April to 31 October 2017 (the 2017 influenza season), 4,359 patients were admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 52% were elderly (≥65 years), 14% were children (<16 years), 6.5% were Aboriginal and Torres Strait Islander peoples, 1.6% were pregnant and 78% had chronic comorbidities. A significant proportion were due to influenza B (31%). Estimated vaccine coverage was 72% in the elderly (≥65 years), 50% in non-elderly adults with medical comorbidities and 24% in children (<16 years) with medical comorbidities. The estimated vaccine effectiveness (VE) in the target population was 23% (95% CI: 7%, 36%). There were a large number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2017, with case numbers more than twice that reported in 2016.


Asunto(s)
Virus de la Influenza B/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Estudios de Casos y Controles , Comorbilidad , Femenino , Hospitalización , Hospitales , Humanos , Virus de la Influenza B/clasificación , Virus de la Influenza B/genética , Gripe Humana/etnología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Grupo de Ascendencia Oceánica , Embarazo , Vigilancia de Guardia , Vacunación , Adulto Joven
19.
Acta Biochim Pol ; 66(3): 329-336, 2019 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-31531422

RESUMEN

The potential emergence of deadly pandemic influenza viruses is unpredictable and most have emerged with no forewarning. The distinct epidemiological and pathological patterns of the Spanish (H1N1), pandemic-2009 (H1N1), and avian influenza (H5N1), known as bird flu, viruses may allow us to develop a 'template' for possible emergence of devastating pandemic strains. Here, we provide a detailed molecular dissection of the structural and nonstructural proteins of this triad of viruses. GenBank data for three representative strains were analyzed to determine the polymorphic amino acids, genetic distances, and isoelectric points, hydrophobicity plot, and protein modeling of various proteins. We propose that the most devastating pandemic strains may have full-length PB1-F2 protein with unique residues, highly cleavable HA, and a basic NS1. Any newly emerging strain should be compared with these three strains, so that resources can be directed appropriately.


Asunto(s)
Simulación por Computador , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/genética , Gripe Aviar/virología , Gripe Humana/virología , Proteínas Virales/química , Animales , Aves , Transmisión de Enfermedad Infecciosa , Genoma Viral , Humanos , Influenza Pandémica, 1918-1919 , Vacunas contra la Influenza , Gripe Aviar/epidemiología , Gripe Aviar/prevención & control , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Pandemias , Conformación Proteica en Hélice alfa , Proteínas Virales/genética
20.
Int J Infect Dis ; 88: 80-87, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31499209

RESUMEN

OBJECTIVES: Eight additional provinces in western China reported human infections for the first time during the fifth wave of human H7N9 infections. The aim of this study was to analyze the epidemiological and virological characteristics of this outbreak. METHODS: The epidemiological data of H7N9 cases from the newly affected western Chinese provinces were collected and analyzed. Full-length genome sequences of H7N9 virus were downloaded from the GenBank and GISAID databases, and phylogenetic, genotyping, and genetic analyses were conducted. RESULTS: The peak of human infections in the newly affected western Chinese provinces was delayed by 4 months compared to the eastern Chinese provinces, and both low pathogenic (LP) and highly pathogenic (HP) H7N9-infected cases were found. The LP- and HP-H7N9 virus belonged to 10 different genotypes (including four new genotypes), of which G11 and G3 were the dominant genotypes, respectively. Almost all of these viruses originated from eastern and southern China and were most probably imported from neighboring provinces. Genetic characteristics of the circulating viruses were similar to those of the viruses from previously affected provinces during Wave Five. CONCLUSIONS: A delayed peak of human infections was observed in the newly affected western Chinese provinces, and reassortment has been ongoing since the introduction of H7N9 viruses. This study highlights the importance of continued surveillance of the circulation and evolution of H7N9 virus in western China.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/virología , China/epidemiología , Brotes de Enfermedades , Genoma Viral , Genotipo , Humanos , Subtipo H7N9 del Virus de la Influenza A/clasificación , Subtipo H7N9 del Virus de la Influenza A/genética , Gripe Humana/epidemiología , Filogenia
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