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1.
Cochrane Database Syst Rev ; 10: CD009927, 2018 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-30288738

RESUMO

BACKGROUND: Engagement in multiple risk behaviours can have adverse consequences for health during childhood, during adolescence, and later in life, yet little is known about the impact of different types of interventions that target multiple risk behaviours in children and young people, or the differential impact of universal versus targeted approaches. Findings from systematic reviews have been mixed, and effects of these interventions have not been quantitatively estimated. OBJECTIVES: To examine the effects of interventions implemented up to 18 years of age for the primary or secondary prevention of multiple risk behaviours among young people. SEARCH METHODS: We searched 11 databases (Australian Education Index; British Education Index; Campbell Library; Cumulative Index to Nursing and Allied Health Literature (CINAHL); Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; Embase; Education Resource Information Center (ERIC); International Bibliography of the Social Sciences; MEDLINE; PsycINFO; and Sociological Abstracts) on three occasions (2012, 2015, and 14 November 2016)). We conducted handsearches of reference lists, contacted experts in the field, conducted citation searches, and searched websites of relevant organisations. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster RCTs, which aimed to address at least two risk behaviours. Participants were children and young people up to 18 years of age and/or parents, guardians, or carers, as long as the intervention aimed to address involvement in multiple risk behaviours among children and young people up to 18 years of age. However, studies could include outcome data on children > 18 years of age at the time of follow-up. Specifically,we included studies with outcomes collected from those eight to 25 years of age. Further, we included only studies with a combined intervention and follow-up period of six months or longer. We excluded interventions aimed at individuals with clinically diagnosed disorders along with clinical interventions. We categorised interventions according to whether they were conducted at the individual level; the family level; or the school level. DATA COLLECTION AND ANALYSIS: We identified a total of 34,680 titles, screened 27,691 articles and assessed 424 full-text articles for eligibility. Two or more review authors independently assessed studies for inclusion in the review, extracted data, and assessed risk of bias.We pooled data in meta-analyses using a random-effects (DerSimonian and Laird) model in RevMan 5.3. For each outcome, we included subgroups related to study type (individual, family, or school level, and universal or targeted approach) and examined effectiveness at up to 12 months' follow-up and over the longer term (> 12 months). We assessed the quality and certainty of evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included in the review a total of 70 eligible studies, of which a substantial proportion were universal school-based studies (n = 28; 40%). Most studies were conducted in the USA (n = 55; 79%). On average, studies aimed to prevent four of the primary behaviours. Behaviours that were most frequently addressed included alcohol use (n = 55), drug use (n = 53), and/or antisocial behaviour (n = 53), followed by tobacco use (n = 42). No studies aimed to prevent self-harm or gambling alongside other behaviours.Evidence suggests that for multiple risk behaviours, universal school-based interventions were beneficial in relation to tobacco use (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.60 to 0.97; n = 9 studies; 15,354 participants) and alcohol use (OR 0.72, 95% CI 0.56 to 0.92; n = 8 studies; 8751 participants; both moderate-quality evidence) compared to a comparator, and that such interventions may be effective in preventing illicit drug use (OR 0.74, 95% CI 0.55 to 1.00; n = 5 studies; 11,058 participants; low-quality evidence) and engagement in any antisocial behaviour (OR 0.81, 95% CI 0.66 to 0.98; n = 13 studies; 20,756 participants; very low-quality evidence) at up to 12 months' follow-up, although there was evidence of moderate to substantial heterogeneity (I² = 49% to 69%). Moderate-quality evidence also showed that multiple risk behaviour universal school-based interventions improved the odds of physical activity (OR 1.32, 95% CI 1.16 to 1.50; I² = 0%; n = 4 studies; 6441 participants). We considered observed effects to be of public health importance when applied at the population level. Evidence was less certain for the effects of such multiple risk behaviour interventions for cannabis use (OR 0.79, 95% CI 0.62 to 1.01; P = 0.06; n = 5 studies; 4140 participants; I² = 0%; moderate-quality evidence), sexual risk behaviours (OR 0.83, 95% CI 0.61 to 1.12; P = 0.22; n = 6 studies; 12,633 participants; I² = 77%; low-quality evidence), and unhealthy diet (OR 0.82, 95% CI 0.64 to 1.06; P = 0.13; n = 3 studies; 6441 participants; I² = 49%; moderate-quality evidence). It is important to note that some evidence supported the positive effects of universal school-level interventions on three or more risk behaviours.For most outcomes of individual- and family-level targeted and universal interventions, moderate- or low-quality evidence suggests little or no effect, although caution is warranted in interpretation because few of these studies were available for comparison (n ≤ 4 studies for each outcome).Seven studies reported adverse effects, which involved evidence suggestive of increased involvement in a risk behaviour among participants receiving the intervention compared to participants given control interventions.We judged the quality of evidence to be moderate or low for most outcomes, primarily owing to concerns around selection, performance, and detection bias and heterogeneity between studies. AUTHORS' CONCLUSIONS: Available evidence is strongest for universal school-based interventions that target multiple- risk behaviours, demonstrating that they may be effective in preventing engagement in tobacco use, alcohol use, illicit drug use, and antisocial behaviour, and in improving physical activity among young people, but not in preventing other risk behaviours. Results of this review do not provide strong evidence of benefit for family- or individual-level interventions across the risk behaviours studied. However, poor reporting and concerns around the quality of evidence highlight the need for high-quality multiple- risk behaviour intervention studies to further strengthen the evidence base in this field.


Assuntos
Consumo de Bebidas Alcoólicas/prevenção & controle , Exercício Físico , Abuso de Maconha/prevenção & controle , Assunção de Riscos , Prevenção do Hábito de Fumar , Transtornos do Comportamento Social/prevenção & controle , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Adolescente , Condução de Veículo , Criança , Pré-Escolar , Terapia Familiar , Humanos , Lactente , Avaliação de Programas e Projetos de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Instituições Acadêmicas , Comportamento Sexual , Adulto Jovem
2.
BMC Public Health ; 18(1): 1180, 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30326897

RESUMO

BACKGROUND: Multiple risk behaviour (MRB) refers to two or more risk behaviours such as smoking, drinking alcohol, poor diet and unsafe sex. Such behaviours are known to co-occur in adolescence. It is unknown whether MRB interventions are equally effective for young people of low and high socioeconomic status (SES). There is a need to examine these effects to determine whether MRB interventions have the potential to narrow or widen inequalities. METHODS: Two Cochrane systematic reviews that examined interventions to reduce adolescent MRB were screened to identify universal interventions that reported SES. Study authors were contacted, and outcome data stratified by SES and intervention status were requested. Risk behaviour outcomes alcohol use, smoking, drug use, unsafe sex, overweight/obesity, sedentarism, peer violence and dating violence were examined in random effects meta-analyses and subgroup analyses conducted to explore differences between high SES and low SES adolescents. RESULTS: Of 49 studies reporting universal interventions, only 16 also reported having measured SES. Of these 16 studies, four study authors provided data sufficient for subgroup analysis. There was no evidence of subgroup differences for any of the outcomes. For alcohol use, the direction of effect was the same for both the high SES group (RR 1.26, 95% CI: 0.96, 1.65, p = 0.09) and low SES group (RR 1.14, 95% CI: 0.98, 1.32, p = 0.08). The direction of effect was different for smoking behaviour in favour of the low SES group (RR 0.83, 95% CI: 0.66, 1.03, p = 0.09) versus the high SES group (RR 1.16, 95% CI: 0.82, 1.63, p = 0.39). For drug use, the direction of effect was the same for both the high SES group (RR 1.29, 95% CI: 0.97, 1.73, p = 0.08) and the low SES group (RR 1.28, 95% CI: 0.84, 1.96, p = 0.25). CONCLUSIONS: The majority of studies identified did not report having measured SES. There was no evidence of subgroup difference for all outcomes analysed among the four included studies. There is a need for routine reporting of demographic information within studies so that stronger evidence of effect by SES can be demonstrated and that interventions can be evaluated for their impact on health inequalities.


Assuntos
Promoção da Saúde , Comportamentos de Risco à Saúde , Disparidades nos Níveis de Saúde , Classe Social , Adolescente , Humanos , Avaliação de Programas e Projetos de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
JMIR Pediatr Parent ; 3(2): e19749, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320100

RESUMO

BACKGROUND: In the United Kingdom, despite some downward trends in alcohol use among young people, over one-fifth of young people reported excessive alcohol use in the past month, which is associated with short- and long-term harm to health. Digital interventions to reduce alcohol use, such as websites, among young people present an appealing and cost-effective mode of intervention that can be integrated into the education system. However, relatively few school-based digital alcohol-focused interventions have been developed and evaluated for young people in the United Kingdom. OBJECTIVE: This study aims to develop a novel web-based intervention, Rethink Alcohol, to prevent and reduce excessive alcohol use and related harm among young people aged between 14 and 15 years, and explore the views of young people, teachers, and youth workers in relation to the content, design, and usability of the intervention. METHODS: Intervention development followed the person-based approach, using theories of social norms and social influence. Qualitative "Think-Aloud" interviews, either one-to-one or paired, were conducted while participants perused and worked through the web-based intervention, talking aloud. Participants included 20 young people (12 female, 8 male), 5 youth workers (4 female, 1 male), 3 teachers (2 male, 1 female), and 1 (male) clinical professional, recruited via youth groups and professional networks. Interviews were audio recorded, transcribed verbatim, and analyzed thematically. RESULTS: The prototype web-based intervention included normative feedback, information, a quiz, interactive activities, and scenarios. On a rating scale of impressions from poor (1) to excellent (5), participants gave an average score of 3.6/5. A total of 5 themes were identified: content, credibility of the website, making the website easy to understand, design and navigation, and suitability for the audience. These themes reflected views that the content was interesting, credible, informative, and embodied a neutral and nonjudgmental tone, but stronger messaging was needed regarding social pressures and short-term risks regarding safety and risk behavior alongside clarity around pathways of risk; credibility and trustworthiness of information were critical features, determined in part, by the professionalism of design and referencing of sources of information provided; and messages should be succinct and come to life through design and interactive features. CONCLUSIONS: Together, the data illustrated the importance and challenge of communicating nuanced alcohol-focused public health messages to young people in concise, clear, nonjudgmental, and appealing ways. Young people report interest in clear, credible, neutral, and interactive messages regarding social pressures and short-term risks of alcohol use via a web-based intervention. There is scope for optimization and feasibility testing of the Rethink Alcohol intervention.

4.
BMJ ; 371: m3934, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33239318

RESUMO

OBJECTIVE: To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization's International Clinical Trials Registry Platform. STUDY SELECTION: Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks. DATA EXTRACTION: Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention. RESULTS: 64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence. CONCLUSIONS: Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049779.


Assuntos
Abstinência de Álcool/psicologia , Alcoolismo/terapia , Terapia Comportamental/métodos , Atenção Primária à Saúde/métodos , Adulto , Alcoolismo/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
5.
Addiction ; 113(11): 2041-2050, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29806869

RESUMO

BACKGROUND AND AIMS: Evidence demonstrating an association between parental alcohol use and offspring alcohol use from robust prospective studies is lacking. We tested the direct and indirect associations between parental and young adult alcohol use via early alcohol initiation, parental monitoring and associating with deviant peers. DESIGN: Prospective birth cohort study. Path analysis was used to assess the possible association between parental alcohol use (assessed at 12 years) and alcohol use in young adults (assessed at 18 years) via potential mediators (assessed at 14 and 15.5 years, respectively). SETTING: South West England. PARTICIPANTS: Data were available on 3785 adolescents and their parents from the Avon Longitudinal Study of Parents and Children. MEASUREMENTS: The continuous Alcohol Use Disorders Identification Test (AUDIT) score was used as the primary outcome measure. Maternal alcohol use was defined as light (< 4 units on any day), moderate (≥ 4 units on 1-3 days) and high-risk (≥ 4 units on ≥ 4 days in 1 week). Partner alcohol use was also defined as light, moderate and high risk. Socio-economic variables were included as covariates. FINDINGS: There was strong evidence of a total effect from maternal alcohol use to young adult alcohol use [moderate: b = 1.07, 95% confidence interval (CI) = 0.64, 1.49, P < 0.001; high risk: b = 1.71, 95% CI = 1.07, 2.35, P < 0.001]. The majority of this association was explained through early alcohol initiation (moderate: b = 0.14, 95% CI = 0.04, 0.25, P = 0.01; high risk: b = 0.24, 95% CI = 0.07, 0.40, P < 0.01) and early alcohol initiation/associating with deviant peers (moderate: b = 0.06, 95% CI = 0.02, 0.10, P < 0.01; high risk: b = 0.10, 95% CI = 0.03, 0.16, P < 0.01). There was strong evidence of a remaining direct effect (moderate: b = 0.81, 95% CI = 0.39, 1.22, P < 0.001; high risk: b = 1.28, 95% CI = 0.65, 1.91, P < 0.001). A similar pattern of results was evident for partner alcohol use. CONCLUSIONS: Young adults whose parents have moderate or high-risk alcohol consumption are more likely to consume alcohol than those with parents with lower alcohol consumption. This association appears to be partly accounted for by earlier alcohol use initiation and higher prevalence of association with deviant peers.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Poder Familiar , Pais , Adolescente , Idade de Início , Criança , Estudos de Coortes , Inglaterra/epidemiologia , Feminino , Humanos , Masculino , Grupo Associado , Estudos Prospectivos , Consumo de Álcool por Menores/estatística & dados numéricos
6.
Syst Rev ; 6(1): 77, 2017 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-28399899

RESUMO

BACKGROUND: Alcohol dependence is common and serious cause of social and physical harm. However, the optimal management of those with moderate and severe alcohol dependence in primary and community care after detoxification remains unclear. The aim of this review is to evaluate the effectiveness of interventions for maintaining abstinence in people with alcohol dependence following detoxification. METHODS: We will systematically search electronic databases and clinical trial registries for randomized controlled trials (RCTs) examining the effectiveness of pharmacological and/or psychosocial interventions for maintaining abstinence in recently detoxified, alcohol-dependent adults. The searches will be complemented by checking references and citations from included studies and other relevant systematic reviews. No limitation on language, year, or publication status will be applied. RCTs will be selected using prespecified criteria. Descriptive information, study characteristics, and results of eligible RCTs will be extracted. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed. DISCUSSION: This network meta-analysis aims to appraise and summarize the total evidence of therapeutic interventions for alcohol-dependent patients that require support for detoxification and can be treated in the community. The evidence will determine which combination of interventions are most promising for current practice and further investigation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049779.


Assuntos
Alcoolismo/terapia , Assistência Ambulatorial/métodos , Metanálise em Rede , Abstinência de Álcool/psicologia , Alcoolismo/psicologia , Humanos , Avaliação de Resultados em Cuidados de Saúde , Revisões Sistemáticas como Assunto
7.
Arch Dis Child ; 101(1): 42-50, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26471110

RESUMO

OBJECTIVE: To undertake a systematic review and meta-analysis to establish the effectiveness of handwashing in reducing absence and/or the spread of respiratory tract (RT) and/or gastrointestinal (GI) infection among school-aged children and/or staff in educational settings. DESIGN: Randomised-controlled trials (RCTs). SETTING: Schools and other settings with a formal educational component in any country. PATIENTS: Children aged 3-11 years, and/or staff working with them. INTERVENTION: Interventions with a hand hygiene component. MAIN OUTCOME MEASURES: Incidence of RT or GI infections or symptoms related to such infections; absenteeism; laboratory results of RT and/or GI infections. RESULTS: Eighteen cluster RCTs were identified; 13 school-based, 5 in child day care facilities or preschools. Studies were heterogeneous and had significant quality issues including small numbers of clusters and participants and inadequate randomisation. Individual study results suggest interventions may reduce children's absence, RT infection incidence and symptoms, and laboratory confirmed influenza-like illness. Evidence of impact on GI infection or symptoms was equivocal. CONCLUSIONS: Studies are generally not well executed or reported. Despite updating existing systematic reviews and identifying new studies, evidence of the effect of hand hygiene interventions on infection incidence in educational settings is mostly equivocal but they may decrease RT infection among children. These results update and add to knowledge about this crucial public health issue in key settings with a vulnerable population. More robust, well reported cluster RCTs which learn from existing studies, are required.


Assuntos
Absenteísmo , Controle de Doenças Transmissíveis/métodos , Doenças Transmissíveis/transmissão , Higiene das Mãos/métodos , Criança , Gastroenteropatias/prevenção & controle , Desinfecção das Mãos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias/prevenção & controle , Infecções Respiratórias/transmissão , Instituições Acadêmicas
8.
Int J Drug Policy ; 25(1): 34-52, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23973009

RESUMO

BACKGROUND: Injecting drug use is a major risk factor for the acquisition and transmission of HIV and Hepatitis C virus (HCV). Prevention of these infections among people who inject drugs (PWID) is critical to reduce ongoing transmission, morbidity and mortality. METHODS: A review of reviews was undertaken involving systematic literature searches of Medline, Embase, CINAHL, PsychINFO, IBSS and the Cochrane Library (2000-2011) to identify English language reviews regarding the effectiveness of harm reduction interventions in relation to HIV transmission, HCV transmission and injecting risk behaviour (IRB). Interventions included needle and syringe programmes (NSP); the provision of injection paraphernalia; opiate substitution treatment (OST); information, education and counselling (IEC); and supervised injecting facilities (SIFs). Reviews were classified into 'core' or 'supplementary' using critical appraisal criteria, and the strength of review-level evidence was assessed. RESULTS: Twelve core and thirteen supplementary reviews were included. From these reviews we identified: (i) for NSP: tentative review-level evidence to support effectiveness in reducing HIV transmission, insufficient review-level evidence relating to HCV transmission, but sufficient review-level evidence in relation to IRB; (ii) for OST: sufficient review-level evidence of effectiveness in relation to HIV transmission and IRB, but tentative review-level evidence in relation to HCV transmission; (iii) for IEC, the provision of injection paraphernalia and SIFs: tentative review-level evidence of effectiveness in reducing IRB; and either insufficient or no review-level evidence for these interventions in relation to HIV or HCV transmission. CONCLUSION: Review-level evidence indicates that harm reduction interventions can reduce IRB, with evidence strongest for OST and NSP. However, there is comparatively little review-level evidence regarding the effectiveness of these interventions in preventing HCV transmission among PWID. Further studies are needed to assess the effectiveness and impact of scaling up comprehensive packages of harm reduction interventions to minimise HIV and HCV transmission among PWID.


Assuntos
Infecções por HIV/prevenção & controle , Redução do Dano , Hepatite C/prevenção & controle , Abuso de Substâncias por Via Intravenosa/complicações , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Programas de Troca de Agulhas , Tratamento de Substituição de Opiáceos , Assunção de Riscos , Abuso de Substâncias por Via Intravenosa/prevenção & controle , Abuso de Substâncias por Via Intravenosa/psicologia
9.
J Med Screen ; 18(4): 204-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22156146

RESUMO

OBJECTIVES: To determine the impact of media reporting of cervical cancer in a UK celebrity on cervical screening uptake, response time and colposcopy referral and attendance. SETTING: Population-based national cervical screening programme for women in Wales, UK. METHODS: A time series regression analysis of the Welsh national cervical screening and colposcopy databases was used to examine the number of smear tests carried out between 2000 and 2010, stratified by age group and deprivation indicators. Logistic regression was used to analyse colposcopy attendance. RESULTS: Over 33,000 more cervical screening tests than expected were carried out in the year of media reporting (2008/9), 11,539 (35%) of which were in the month of Jade Goody's death. The largest increase was evident in women aged 35-39 years (475 additional tests per month, 95% CI 331-619). Impacts were similar across deprivation quintiles. Colposcopy referrals increased by 18% during the year of media reporting. Increases were observed for all smear test results in 2008/9, particularly among younger women, and further rises were evident in 2009/10 for smear tests showing borderline changes and mild dyskaryosis. The proportion of women attending colposcopy appointments rose in the year of media reporting (χ(2) = 45.8, P < 0.001). CONCLUSIONS: Mass media reporting of cervical cancer in a UK celebrity was associated with a significant, but transient, increase in screening uptake and colposcopy referral and attendance. Mass media reporting can play a role in enhanced detection of abnormalities, but public health messages must be communicated effectively to minimize anxiety whilst maximizing case-finding and uptake among non-responders.


Assuntos
Programas de Rastreamento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Colposcopia/estatística & dados numéricos , Pessoas Famosas , Feminino , Humanos , Meios de Comunicação de Massa , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/tendências , Programas Nacionais de Saúde , Encaminhamento e Consulta/estatística & dados numéricos , Análise de Regressão , Mudança Social , Reino Unido/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , País de Gales/epidemiologia
10.
J Virol ; 81(9): 4766-75, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17314172

RESUMO

Most humans carry Epstein-Barr virus (EBV) in circulating memory B cells as a latent infection that is controlled by an immune response. When infected by EBV, B lymphocytes in fetal cord blood are readily transformed to lymphoblastoid cell lines (LCL). It is frequently assumed that this high efficiency of transformation is due to the absence of a primary immune response. However, cord blood lymphocytes stimulated with autologous LCL yield CD4+ T cells that can completely inhibit the growth of LCL by a major histocompatibility complex-restricted cytotoxic mechanism mediated by granulysin and granzyme B. Because EBV-transformed B cells maintain the phenotype of antigen-activated B-cell blasts, they can potentially receive inhibitory or helper functions from CD4+ T cells. To assess these functions, the effect of EBV-specific CD4+ T cells on the efficiency of virus transformation of autologous B cells was assayed. Paradoxically, although the cytotoxic CD4+ T-cell lines reduced EBV B-cell transformation at a high effector/target ratio of 10:1, they caused a twofold increase in B-cell transformation at the lower effector/target ratio of 1:1. Th1-polarized CD4+ T cells were more effective at inhibiting B-cell transformation, but Th2-polarized cell lines had reduced cytotoxic activity, were unable to inhibit LCL growth, and caused a 10-fold increase in transformation efficiency. Tonsil lymphoid follicles lacked NK cells and CD8+ T cells but contained CD4+ T cells. We propose that CD4+ T cells provide helper or cytotoxic functions to EBV-transformed B cells and that the balance of these functions within tonsil compartments is critical in establishing asymptomatic primary EBV infection and maintaining a stable lifelong latent infection.


Assuntos
Linfócitos B/imunologia , Citotoxicidade Imunológica/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Sangue Fetal/imunologia , Herpesvirus Humano 4/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos B/citologia , Linfócitos B/virologia , Linhagem Celular , Sangue Fetal/virologia , Citometria de Fluxo , Humanos , Microscopia de Fluorescência , Tonsila Palatina/imunologia , Tonsila Palatina/virologia , Linfócitos T Auxiliares-Indutores/virologia
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