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Cardiovascular diseases (CVD) are the leading cause of death worldwide and they disproportionally affect people living in disadvantaged communities. Nurse-led behaviour change interventions have shown great promise in preventing CVD. However, knowledge regarding the impact and nature of such interventions in disadvantaged communities is limited. This review aimed to address this knowledge gap. A six-stage scoping review framework developed by Arksey and O'Malley, with revisions by Levac et al., was used. The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews (PRISMA-ScR). Three electronic databases were searched (PUBMED/MEDLINE, CINAHL Plus, and Cochrane CENTRAL), and included studies were analysed using Braun and Clarke's 'Thematic Analysis' approach. Initial searches yielded 952 papers and 30 studies were included in the review following duplicate, title/abstract, and full-text screening. The included studies indicate that nurse-led behaviour change primary prevention interventions in disadvantaged areas are largely effective; albeit the considerable variety of intervention approaches, study populations and outcome measures used to date make it difficult to ascertain this. Other identified key areas in the promotion of nurse-led behaviour change included tailoring interventions to specific populations, providing adequate training for nurses, overcoming patient access difficulties and encouraging patient engagement. Overall, the findings indicate that nurse-led behaviour change interventions for high-risk CVD patients in disadvantaged areas show much promise, although there is considerable variety in the interventions employed and studied to date. Further research is needed to examine the unique barriers and facilitators of interventions for specific disadvantaged groups.
Assuntos
Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/prevenção & controle , Papel do Profissional de Enfermagem , Populações VulneráveisRESUMO
Although traditional egg-based inactivated influenza vaccines can protect against infection, there have been significant efforts to develop improved formats to overcome disadvantages of this platform. Here, we have assessed human CD4 T cell responses to a traditional egg-based influenza vaccine with recently available cell-derived vaccines and recombinant baculovirus-derived vaccines. Adults were administered either egg-derived Fluzone®, mammalian cell-derived Flucelvax® or recombinant HA (Flublok®). CD4 T cell responses to each HA protein were assessed by cytokine EliSpot and intracellular staining assays. The specificity and magnitude of antibody responses were quantified by ELISA and HAI assays. By all criteria, Flublok vaccine exhibited superior performance in eliciting both CD4 T cell responses and HA-specific antibody responses, whether measured by mean response magnitude or percent of responders. Although the mechanism(s) underlying this advantage is not yet clear, it is likely that both qualitative and quantitative features of the vaccines impact the response.
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We conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42-63] and 35% in Marshfield (95% CI 28-42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter.
Assuntos
Infecções Respiratórias/epidemiologia , Viroses/epidemiologia , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Estudos Prospectivos , Infecções Respiratórias/virologia , Estações do Ano , Viroses/virologia , Wisconsin/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Based on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60-64 years of age have been published. The same study also included a cohort of adults aged 18-49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18-49 years of age compared with adults 60-64 years of age for whom PCV13 is approved. METHODS: Adults naive to PPSV23 were grouped by age into 2 cohorts: 18-49 years (n=899; further stratified by age into 3 subgroups 18-29, 30-39, and 40-49 years) and 60-64 years (n=417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated. RESULTS: In adults aged 18-49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60-64 years. Immune responses were highest in the youngest age subgroup (18-29 years). Local reactions and systemic events were more common in adults 18-49 years compared with 60-64 years and were self-limited. CONCLUSION: Immune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections.
Assuntos
Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Estudos de Coortes , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Proteínas Opsonizantes/sangue , Fagocitose , Vacinas Pneumocócicas/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
Bison (Bison bison) and elk (Cervus elaphus) in the greater Yellowstone ecosystem have long been infected with Brucella abortus. The continued culling of large numbers of Yellowstone bison to reduce the risk of brucellosis transmission to cattle could negatively affect long-term conservation. A desirable management objective is to reduce the level of B. abortus infection while conserving wildlife populations. Identifying the ecological factors that influence immune suppression and vulnerabilityto infection will help initiate effective control measures. Seasonal food restriction during pregnancy has the potential to limit resources available for immune defence and may be an important factor sustaining brucellosis in wild ungulate populations. Consequently, effective management practices will need to include a diverse range of integrated methods, which include maintaining separation of livestock and wildlife, managing habitat to reduce brucellosis transmission, and reducing disease prevalence in wildlife. The long-term success of these management practices will depend on sound science and support of the stakeholders involved.
Assuntos
Animais Selvagens , Bison , Brucelose/veterinária , Conservação dos Recursos Naturais/métodos , Cervos , Ecossistema , Animais , Brucelose/epidemiologia , Brucelose/prevenção & controle , Privação de Alimentos , Estações do Ano , Estados Unidos/epidemiologiaRESUMO
Eradication of brucellosis from bison (Bison bison) and elk (Cervus elaphus) populations in the Greater Yellowstone Area is not possible with current technology. There are considerable uncertainties regarding the effectiveness of management techniques and unintended effects on wildlife behaviour and demography. However, adaptive management provides a framework for learning about the disease, improving suppression techniques, and lowering brucellosis transmission among wildlife and to cattle. Since it takes approximately three years after birth for female bison to become reproductively active and contribute to brucellosis transmission, there is an opportunity to implement actions such as vaccination and the selective removal of infectious bison based on age and assay results to reduce the potential for transmission. Older adult bison that have been exposed to the bacteria, but recovered from acute infection, could be retained in the population to provide some immunity (resistance) against future transmission. Through careful predictions, research, and monitoring, our understanding and technology will be improved and management actions can be adjusted to better achieve desired outcomes.
Assuntos
Bison , Brucella abortus , Brucelose/veterinária , Conservação dos Recursos Naturais/métodos , Cervos , Animais , Animais Selvagens , Vacina contra Brucelose/imunologia , Brucelose/epidemiologia , Brucelose/prevenção & controle , Vigilância da População , Estudos Soroepidemiológicos , Estados Unidos/epidemiologiaRESUMO
Alternative substrates for influenza vaccine production are needed to ensure adequate supplies. We evaluated the relative safety and immunogenicity of recombinant hemagglutinin (rHA) or trivalent inactivated vaccine (TIV) among 869 > or =65-year-old subjects in a randomized clinical trial. Virologic surveillance for influenza-like illness (ILI) was conducted during the 2006-2007 epidemic. Vaccines were well tolerated. Seroconversion rates vs. influenza A/H1N1 and H3N2 antigens were superior in the rHA group, but were inferior vs. influenza B; however, results for influenza B are confounded since the vaccine antigens were different. ILI frequencies were low and similar in both groups. Studies assessing relative immunogenicity of vaccines using identical B Ags are warranted.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vacinas contra Influenza/imunologia , Proteínas Recombinantes/imunologia , Idoso , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Estudos Multicêntricos como Assunto , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologiaRESUMO
BACKGROUND: Influenza is a potentially life-threatening illness that affects approximately 10% of the population annually, with resulting personal misery and societal disruption. Oseltamivir is a novel influenza treatment that has been extensively investigated. We describe a series of retrospective analyses investigating various measures of clinical efficacy across different populations of influenza-infected patients enrolled in studies of oseltamivir (Tamiflu((R))) that were conducted within the clinical development programme. METHODS: Adolescents and adults (13-97 years, n = 4015) presenting within 36 hours of onset of influenza symptoms were randomised to receive oseltamivir 75mg or placebo twice daily for 5 days during local influenza outbreaks. Of these patients, 2413 had laboratory-confirmed influenza and are included in the analysis. Approximately 30% (n = 739) of patients were 'high risk'; 20% were healthy elderly subjects (n = 488) and 10% (n = 251) were patients with chronic respiratory and/or cardiac conditions. The primary endpoint was time to alleviation of a seven-symptom cluster in influenza-infected patients. Supplementary analyses were conducted using a variety of illness definitions and symptom clusters to investigate the sensitivity of the assessment of overall efficacy to differing disease definitions and also to explore efficacy in important subpopulations. RESULTS: A total of 2413 patients had confirmed influenza infection (placebo: n = 1063; oseltamivir: n = 1350). Across all populations, the time to alleviation of illness was reduced by 19% (median duration 100.6 hours [95% CI 94.8-104.7]) compared with placebo (124.5 hours [95% CI 117.7-132.3], p < 0.0001). Oseltamivir recipients returned to normal health status, regained ability to perform usual activities and regained normal sleep patterns significantly faster than placebo recipients. The median duration of troublesome influenza symptoms was significantly reduced by oseltamivir treatment, e.g. fatigue by 29% and myalgia by 26% (both p < 0.0001). After 48 hours of treatment, 57% more placebo than oseltamivir recipients remained febrile, despite greater use of acetaminophen by placebo recipients. In addition, the median duration of acute febrile illness was significantly shortened by oseltamivir treatment compared with placebo in patients with cardiac disease (44.0 hours vs 64.7 hours, p = 0.026) or chronic obstructive airways disease (37.9 hours vs 53.8 hours, p = 0.004).Efficacy was similar among influenza A- and influenza B-infected patients. Oseltamivir was well tolerated, with transient gastrointestinal effects (observed in one in seven oseltamivir-treated patients compared with one in 12 patients on placebo) that only rarely resulted in study discontinuation. CONCLUSIONS: Oral oseltamivir is a well tolerated and effective treatment for influenza in adolescents and adults, including the elderly and patients with chronic cardiac and/or respiratory disease.
RESUMO
Intranasal administration of laboratory passaged wild-type influenza viruses to adults induces a mild upper respiratory illness accompanied by nasopharyngeal shedding of virus. A second model has used inoculation of children with attenuated viruses as a surrogate for wild-type infection. Generally, results of studies of antiviral or vaccine approaches in the challenge model have been predictive of efficacy in the real world, but it is recognized that the model does not reproduce naturally acquired illness well and both viral shedding and symptoms in the challenge model are mostly restricted to the upper respiratory tract. Serum antibody plays a major role in protection in this model and it is difficult to infect adults who have serum HI titres of > 1:8. Among adults with lower levels of HI antibody, a variety of protective factors have been described, including nasal IgA and serum NI antibody, and CTL. In some challenge studies, subjects have been protected despite lack of a measurable immune response to vaccination. Because measurement of mucosal antibody has been difficult to standardize, there is not a level that can be considered a cut-off for susceptibility. Use of a consistent method for assessing mucosal IgA between studies may help to derive a target level for vaccination.
Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adulto , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/imunologiaRESUMO
Joining polysaccharide antigens to protein increases immunogenicity in infants. In older adults, using conjugation to protein carriers to improve the immune response to pneumococcal polysaccharide vaccine has thus far proved disappointing. Low immunity to the carrier protein in the elderly may explain the failure of conjugated vaccines to elicit a T-cell-dependent response. We immunized 49 older adults (ages 60-78) and 50 younger adults (ages 18-45) with either 23-valent pneumococcal polysaccharide (PS) vaccine or 5-valent CRM197-conjugated pneumococcal oligosaccharide. Sera obtained before and after vaccination were analyzed for antibody to pneumococcal serotypes 14 and 6B and diphtheria toxin by ELISA. Baseline diphtheria toxin antibody level was lower in older adults than in younger adults (0.31 and 0.88 IU/ml, respectively; p < 0.0001). Adults with higher diphtheria antibody level had a higher antibody level to PS type 6B after vaccination than those with lower diphtheria antibody level (9.9 vs. 3.5 microg/ml, respectively; p = 0.01). Antibody level to PS type 14 was higher, but differed by baseline anti-diphtheria antibody level only when the older group was evaluated alone. Low levels of antibody to diphtheria protein may explain some of the lower responses to conjugate pneumococcal vaccine in older adults.
Assuntos
Anticorpos Antibacterianos/sangue , Corynebacterium diphtheriae/imunologia , Infecções Pneumocócicas/tratamento farmacológico , Vacinas Pneumocócicas/uso terapêutico , Adulto , Idoso , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Vanilloid receptor subtype 1 (VR1) is a ligand-gated channel that can be activated by capsaicin and other vanilloids as well as by protons and heat. In the present study, we have analyzed the oligomeric state of VR1. Co-immunoprecipitation of differently tagged VR1 molecules indicated that VR1 can form oligomers. Using two different heterologous VR1 expression systems as well as endogenous VR1 expressed in dorsal root ganglion cells, we analyzed oligomer formation using perfluoro-octanoic acid polyacrylamide gel electrophoresis. Results were confirmed both with chemical cross-linking agents as well as through endogenous cross-linking mediated by transglutaminase. Our results clearly show that VR1 forms multimers in each of the expression systems with a homotetramer as a predominant form. The oligomeric structure of VR1 may contribute to the complexity of VR1 pharmacology. Finally, differences in glycosylation between the systems were observed, indicating the need for caution in the use of the heterologous expression systems for analysis of VR1 properties.
Assuntos
Receptores de Droga/química , Animais , Western Blotting , Células CHO , Células COS , Caprilatos/química , Cricetinae , Reagentes de Ligações Cruzadas/farmacologia , Dimerização , Relação Dose-Resposta a Droga , Eletroforese em Gel de Poliacrilamida , Fluorocarbonos/química , Proteínas de Fluorescência Verde , Ligantes , Proteínas Luminescentes/metabolismo , Plasmídeos/metabolismo , Testes de Precipitina , Estrutura Quaternária de Proteína , Prótons , Proteínas Recombinantes de Fusão/metabolismo , Canais de Cátion TRPV , Transfecção , Transglutaminases/metabolismoRESUMO
Recent outbreaks of avian influenza in humans have demonstrated the need for vaccines for influenza viruses with pandemic potential. Recombinant hemagglutinins are an attractive option for such vaccines because they do not require handling potentially highly pathogenic influenza viruses for vaccine production. In order to evaluate the immunogenicity, optimum dosing and timing of administration of a recombinant baculovirus-expressed H5 HA (rH5) in humans, 147 healthy adults were assigned randomly to receive intramuscular rH5 as two doses of 25, 45 or 90 microg each, one dose of 90 microg followed by a dose of 10 microg, or two doses of placebo, at intervals between doses of 21, 28 or 42 days. All doses of rH5 were well tolerated. The rH5 vaccine was modestly immunogenic at high dose. Neutralizing antibody responses to a titer of 1:80 or greater were seen in 23% (14/60) of individuals after a single dose of 90 microg, and in 52% (15/29) after two doses of 90 microg. Varying intervals between doses from 21 to 42 days had no significant effect on antibody responses to vaccination. These results suggest that baculovirus-expressed H5 HA can induce functional antibody in individuals who have not had prior exposure to H5 viruses, but that further studies to improve the immunogenicity of the vaccine are needed.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto , Anticorpos Antivirais/imunologia , Relação Dose-Resposta Imunológica , Ensaio de Imunoadsorção Enzimática , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Esquemas de Imunização , Cinética , Testes de Neutralização , VacinaçãoRESUMO
Influenza epidemics account for more than 20,000 deaths in the United States each year, as well as substantial morbidity, medical costs, and time away from work and school. Since the 1950s, the principal weapon against these seasonal epidemics has been killed virus vaccine formulations. Despite massive efforts to immunize at-risk individuals against influenza, not everyone receives the vaccine. In addition, use of some drugs, such as amantadine and rimantadine, can lead to the development of drug resistant viruses in infected individuals and to transmission of these viruses to susceptible individuals. The many factors that contribute to the high annual incidence of influenza virus infections mandate prompt clinical recognition and appropriate patient management. Rapid diagnostic tests have been developed that may make it possible to avoid the use of antibacterial drugs, quickly decide whether isolation of infected patients is needed, and discharge hospitalized patients sooner.
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Influenza Humana/diagnóstico , Febre/virologia , Imunofluorescência , Humanos , Influenza Humana/virologia , Orthomyxoviridae/isolamento & purificação , Testes SorológicosRESUMO
We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand family that is functionally involved in B cell proliferation. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune disease. Here, we describe expression cloning of a cell surface receptor for TALL-1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is identical to the previously reported TNF receptor (TNFR) homologue transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human and murine TACI share 54% identity overall. Human TACI exhibits high binding affinities to both human and murine TALL-1. Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In addition, when injected into mice, soluble TACI inhibits antibody production to both T cell-dependent and -independent antigens. By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation. The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus.
Assuntos
Linfócitos B/imunologia , Proteínas de Membrana/fisiologia , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/imunologia , Fator de Necrose Tumoral alfa/fisiologia , Sequência de Aminoácidos , Animais , Fator Ativador de Células B , Linfoma de Burkitt , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Biblioteca Gênica , Humanos , Ligantes , Ativação Linfocitária , Linfoma de Células B , Camundongos , Dados de Sequência Molecular , Receptores do Fator de Necrose Tumoral/química , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Proteína Transmembrana Ativadora e Interagente do CAML , Células Tumorais CultivadasAssuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Endopeptidases/metabolismo , Norbornanos/síntese química , Inibidores de Proteases/síntese química , Sulfonamidas/síntese química , Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides/biossíntese , Ácido Aspártico Endopeptidases , Linhagem Celular , Humanos , Norbornanos/química , Inibidores de Proteases/química , Relação Estrutura-Atividade , Sulfonamidas/químicaRESUMO
CONTEXT: Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza. OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection. DESIGN: Randomized, placebo-controlled, double-blind study conducted January through March 1998. SETTING: Sixty primary care and university health centers throughout the United States. PARTICIPANTS: A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. INTERVENTIONS: Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209). MAIN OUTCOME MEASURES: Duration and severity of illness in individuals infected with influenza. RESULTS: Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001). CONCLUSIONS: Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.
Assuntos
Acetamidas/uso terapêutico , Antivirais/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Influenza Humana/tratamento farmacológico , Neuraminidase/antagonistas & inibidores , Acetamidas/administração & dosagem , Doença Aguda , Adulto , Antivirais/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Influenza Humana/complicações , Influenza Humana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oseltamivir , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.
Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Temperatura Baixa , Testes de Inibição da Hemaglutinação , Humanos , Imunoglobulina A/sangue , Lactente , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Macaca mulatta , Vacinação , Vacinas Atenuadas/imunologiaRESUMO
Inactivated influenza vaccine (Ivac) has had an important impact on reducing attack rates of influenza and reducing the severity of illness amongst the vaccinees who still acquire infection. Ivac is most efficacious amongst young, otherwise healthy subjects and least effective against elderly at high risk. This is in part because Ivac does not appear to significantly reduce infection rates and in part because response rate and final antibody titer are lower in the elderly. Therefore Ivac does not eliminate disease in the elderly who are prone to complications when any virus replication occurs. Simultaneous administration of intra-nasal live attenuated influenza vaccine (Livac) and Ivac reduces the infection rate and thus illness rate amongst high-risk elderly. Presumably this is because of the ability of Livac to stimulate secretory antibody which neutralizes virus at the mucosal surface. Other approaches are examining the benefit of baculovirus recombinant vaccine or adjuvanted Ivac to determine if the higher serum antibody these vaccines produce compared to Ivac, will diffuse onto the mucosal surfaces and in a similar fashion, neutralize virus at that site.
Assuntos
Vacinas contra Influenza/farmacologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Idoso , Envelhecimento/imunologia , Anticorpos Antivirais/sangue , Baculoviridae/genética , Método Duplo-Cego , Humanos , Imunidade nas Mucosas , Vacinas contra Influenza/administração & dosagem , Pessoa de Meia-Idade , Orthomyxoviridae/imunologia , Segurança , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/farmacologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/farmacologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/farmacologiaRESUMO
OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.
Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Vacinação , Administração Intranasal , Criança , Pré-Escolar , Temperatura Baixa , Método Duplo-Cego , Feminino , Humanos , Vírus da Influenza B/imunologia , Masculino , Estudos Prospectivos , Vacinas AtenuadasRESUMO
Fifty-seven human immunodeficiency virus (HIV)-infected (CDC class A1-2) and 54 non-HIV-infected adults, not prescreened for influenza susceptibility, were randomized to receive trivalent live attenuated influenza vaccine (LAIV) or placebo intranasally. LAIV was safe and well tolerated with no serious adverse events attributable to vaccine. Reactogenicity rates were similar in LAIV and placebo recipients except that runny nose/nasal congestion was significantly more common in LAIV recipients regardless of HIV status. No prolonged shedding of LAIV was observed in HIV-infected participants. HIV RNA levels were not increased and CD4 counts were not decreased in HIV-infected LAIV recipients compared with placebo recipients after immunization. Shedding of LAIV and increases in antibody titers were infrequent, consistent with prior experience in unscreened adults. The data suggest that inadvertent vaccination with LAIV in relatively asymptomatic HIV-infected adults would not be associated with frequent significant adverse events.