2013-2014年度季节性流行性感冒疫苗对儿童保护效果的病例对照研究

目的 评价2013-2014年度季节性流行性感冒疫苗（流感疫苗）对6~59月龄儿童的保护效果。方法 选择2013-2014年度6~59月龄的实验室诊断流感病例为病例组,在广州市免疫规划系统中随机选择健康儿童为对照组,进行成组病例对照研究,采用非条件Logistic回归计算保护效果。结果 本研究共纳入2 690名研究对象。2013-2014年度,流感疫苗对6~59月龄儿童的保护效果为42.3%（95% CI：27.8%~53.8%）,对36~59月龄儿童的保护效果高于6~35月龄儿童,完全免疫的保护效果高于部分免疫,性别间保护效果无统计学差异。结论 流感疫苗对6~59月龄儿童具有中等保护效果,建议6~59月龄儿童每年接种流感疫苗。     

Case-control vaccine effectiveness studies: Data collection,analysis and reporting results

The case-control methodology is frequently used to evaluate vaccine effectiveness post-licensure. The results of such studies provide important insight into the level of protection afforded by vaccines in a ‘real world’ context, and are commonly used to guide vaccine policy decisions. However, the potential for bias and confounding are important limitations to this method, and the results of a poorly conducted or incorrectly interpreted case-control study can mislead policies. In 2012, a group of experts met to review recent experience with case-control studies evaluating vaccine effectiveness; we summarize the recommendations of that group regarding best practices for data collection, analysis, and presentation of the results of case-control vaccine effectiveness studies. Vaccination status is the primary exposure of interest, but can be challenging to assess accurately and with minimal bias. Investigators should understand factors associated with vaccination as well as the availability of documented vaccination status in the study context; case-control studies may not be a valid method for evaluating vaccine effectiveness in settings where many children lack a documented immunization history. To avoid bias, it is essential to use the same methods and effort gathering vaccination data from cases and controls. Variables that may confound the association between illness and vaccination are also important to capture as completely as possible, and where relevant, adjust for in the analysis according to the analytic plan. In presenting results from case-control vaccine effectiveness studies, investigators should describe enrollment among eligible cases and controls as well as the proportion with no documented vaccine history. Emphasis should be placed on confidence intervals, rather than point estimates, of vaccine effectiveness. Case-control studies are a useful approach for evaluating vaccine effectiveness; however careful attention must be paid to the collection, analysis and presentation of the data in order to best inform evidence-based vaccine policies.     

2009-2013年南京市流感流行病学特征分析

目的 描述2009-2013年期间南京市流感的流行病学规律和特点。方法 流感样本来源于流感样病例,利用逆转录聚合酶链反应确定阳性病例以及流感分型。采用Excel 2007整理数据和SPSS 19.0进行统计分析。结果 2009-2013年间,南京地区共有流感样病例17 906例,其中阳性2 990例,流感阳性率为16.7%。流感阳性率随月份、季度和年份而改变,南京阳性率高峰主要出现在秋冬季,也伴有一些夏季的高峰。甲型流感主要在夏季、秋季和冬季流行,乙型流感主要在冬季流行。2009-2013年南京优势毒株为甲型H1N1,H3N2和乙型流感。H3N2通常在秋季和夏季达到流行高峰,甲型H1N1大流行在秋季出现高峰,乙型流感主要在冬季流行。南京地区在秋季和初冬出现流行高峰,但有些年份,在夏季和初秋出现H3N2流行高峰。采用移动流行病学方法建立标准模型,一般流感在南京的流行大约持续11周,流行阈值为25.21%,流感阳性的背景率为5.82%。结论 南京流感高峰通常一年发生一次,但在有些年份中,会出现两个流感高峰时期。     

流感病毒RT-PCR核酸检测及流行病学特点

目的流感网络监测实验室对辖区内采集的流感样病例咽拭子标本进行流感病毒RT-PCR核酸检测,并对检测结果进行流行病学分析,以进一步掌握流感的流行规律,为制订有效的流感防控措施提供依据。方法自2009年9月～2010年2月,由哨点医院和辖区内各疾病预防控制中心采集的流感样病例咽拭子标本,用RT-PCR方法进行流感病毒核酸检测。并且从不同地区、年龄、性别、时间分布以及流感各亚型等多方面对检测结果进行比较分析。结果检测流感样病例咽拭子标本457份,从时间分布来看,甲型H1N1从2009年9月～2010年1月均有阳性病例,2009年11月和12月阳性率达到了43.6%和42.9%,而乙型流感每个月都有阳性病例,在2009年阳性率均在10%以下,2010年却超过了10%。从年龄分布来看,各型流感的发病人群主要为5～49岁年龄段,其阳性率为42.2%。哨点医院低于疫情采样的甲型H1N1流感检测阳性率,而季节性H1、季节性H3、A未分型以及乙型流感的阳性率与疫情采样均无差别。结论六安市半年来流感疫情以甲型H1N1为主,甲型H1N1流感病例逐渐降低,而乙型流感病例逐渐上升,流感的流行渐趋缓和。流感的发病人群以5～49岁年龄段为主,是流感防控的重点人群。     

Case-control vaccine effectiveness studies: Preparation,design, and enrollment of cases and controls

Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under ‘real world’ conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential.     

Influenza vaccine effectiveness in Italy: Age,subtype-specific and vaccine type estimates 2014/15 season

The 2014/15 influenza season in Europe was characterised by the circulation of influenza A(H3N2) viruses with an antigenic and genetic mismatch from the vaccine strain A/Texas/50/2012(H3N2) recommended for the Northern hemisphere for the 2014/15 season. Italy, differently from other EU countries where most of the subtyped influenza A viruses were H3N2, experienced a 2014/15 season characterized by an extended circulation of two influenza viruses: A(H1N1)pdm09 and A(H3N2), that both contributed substantially to morbidity.Within the context of the existing National sentinel influenza surveillance system (InfluNet) a test-negative case-control study was established in order to produce vaccine effectiveness (VE) estimates. The point estimates VE were adjusted by age group (<5; 5–15; 15–64; 65+ years), the presence of at least one chronic condition, target group for vaccination and need help for walking or bathing. In Italy, adjusted estimates of the 2014/15 seasonal influenza VE against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza for all age groups were 6.0% (95%CI: −36.5 to 35.2%), 43.6% (95%CI: −3.7 to 69.3%), −84.5% (95%CI: (−190.4 to −17.2%) and 50.7% (95% CI: −2.5 to 76.3%) against any influenza virus, A(H1N1)pdm09, A(H3N2) and B, respectively. These results suggest evidence of good VE against A(H1N1)pdm09 and B viruses in Italy and evidence of lack of VE against A(H3N2) virus due to antigenic and genetic mismatch between circulating A(H3N2) and the respective 2014/15 vaccine strain.     

Interim influenza vaccine effectiveness: A good proxy for final estimates in Spain in the seasons 2010–2014

IntroductionThe agreement between interim and final influenza vaccine effectiveness (VE) estimates would support the use of interim assessments as a proxy for final VE results to guide health authorities in influenza prevention. We aimed to compare interim/final VE estimates in Spain.MethodsWe used a test-negative case-control study (cycEVA) for 2010/11–2013/14 seasons. Sensitivity analyses were carried out by type/subtype of influenza virus and by target groups for vaccination.ResultsIn general, interim estimates were higher compared to end-season estimates. Interim and final VE differences were higher for the target groups compared to all population. Subtype-specific interim/final VE estimates showed greater concordance (3–13%) than for any virus (7–24%).ConclusionIn Spain, interim influenza VE estimates over 2010–2014 were a good proxy of the final protection of the vaccine. Interim and final estimates showed greater concordance for all population and if performed subtype-specific.     

淮北市2009～2011年流感病原学监测结果分析

目的通过采集流感样病例咽拭子标本进行流感病毒核酸检测,并对检测结果进行流行病学分析,了解流感的流行规律,为制定有效的防控措施提供依据。方法2009年9月-2011年2月,由哨点医院采集流感样病例咽拭子标本,用RT—PCR方法进行流感病毒核酸检测。结果淮北市2009～2011年12月共检测流感样病例咽拭子1620份,核酸阳性标本242例,阳性率为14．94％。其中,甲型H1N1196例,主要集中在2009年8月～12月;季节性H12例,季节性H334例,B型流感病毒10例。结论2009—2011年流感监测结果显示,2009～2011年,淮北市流感疫情以甲型H1N1为主,伴有甲型H3亚型和乙型散发。流感的发病人群以5—59岁年龄段为主,是流感防控的重点人群。     

Immunogenicity and safety of a cell culture-derived inactivated trivalent influenza vaccine (NBP607): A randomized,double-blind,multi-center,phase 3 clinical trial

BackgroundCell culture-derived influenza vaccines (CCIVs) have several important advantages over egg-based influenza vaccines, including shorter production time, better preservation of wild-type virus antigenicity and large-scale production capacity.MethodsA randomized, double-blind, phase 3 trial was undertaken to evaluate the immunogenicity and safety of a novel cell culture-derived inactivated, subunit, trivalent influenza vaccine (NBP607, SK Chemicals, Seongnam, Korea) compared to the control vaccine (Agrippal^®S1, Novartis Vaccines and Diagnostics Srl, Siena, Italy) among healthy adults aged 19 years or older (Clinical trial Number—NCT02344134). Immunogenicity was determined at pre-vaccination, 1 month and 6 month post-vaccination by the hemagglutination inhibition assay. Solicited and unsolicited adverse events were assessed after vaccination.ResultsA total of 1156 healthy subjects were recruited. NBP607 met all of the criteria of Committee for Medicinal Products for Human Use (CHMP) at 21 days post-vaccination. Contrary to NBP607, the control vaccine did not satisfy the seroconversion criteria for influenza B irrespective of age. Although the geometric mean titer for each influenza subtype declined gradually, seroprotection rate still remained ≥80% for all subtypes up to six month after NBP607 administration. NBP607 recipients met the seroprotection criteria for all three influenza subtypes up to 6 month post-vaccination. There was no significant difference in the occurrence of adverse events between the NBP607 and control groups.ConclusionNBP607, a novel CCIV, showed excellent immunogenicity that lasted ≥6 months after vaccination and had tolerable safety profiles. In particular, NBP607 was more immunogenic against influenza B compared to the control, an egg-based subunit vaccine.     

逆转录聚合酶链反应法在北京市流感病毒型别鉴定中的应用

目的：建立在流感病毒型别鉴定中使用的逆转录聚合酶链反应（RT－PCR）法。方法：用常规细胞培养法扩增病毒后,用2对型别鉴定引物和4对亚型鉴定引物进行RT－PCR反应。结果：在23株发生细胞病理变化的标本中RT－PCR阳性标本为10份,其中甲型7株（6株甲3亚型、1株甲1亚型）,乙型3株,结论：该方法快速、特异,灵敏,在流感病毒型别鉴定中具有较大的应用价值。     

Intraseason decline in influenza vaccine effectiveness during the 2016 southern hemisphere influenza season: A test-negative design study and phylogenetic assessment

Background

We estimated the effectiveness of seasonal inactivated influenza vaccine and the potential influence of timing of immunization on vaccine effectiveness (VE) using data from the 2016 southern hemisphere influenza season.

Seasonal influenza vaccine efficacy and its determinants in children and non-elderly adults: A systematic review with meta-analyses of controlled trials

Context

The true level of influenza vaccine efficacy is controversial and many factors may influence its estimation.

Objectives

To estimate the efficacy of vaccination of children and non-elderly adults for the prevention of influenza and to explore the impact of type of vaccine, age, degree of strain matching, influenza type and case ascertainment methods on vaccine efficacy estimates.

Data sources

Medline and EmBase databases until October 2011. References of relevant articles were also reviewed.

Study selection

Controlled trials evaluating seasonal influenza vaccines and presenting incidence of laboratory-confirmed influenza illness were eligible. Studies exploring efficacy after experimental challenge, presenting duplicate data, employing group randomization, or focusing on special populations were excluded.

Data extraction

The vaccine effect on influenza prevention was evaluated by calculating Mantel–Haenszel risk ratios (RR) and using random-effects models. Vaccine efficacies were calculated for each comparison as (1 − RR) × 100.

Results

Thirty studies were included in one or more of a total of 101 analyses, comprising 88.468 study participants. There was evidence of heterogeneity in 49% of the analyses. Summary vaccine efficacy was 65% against any strain, 78% against matched strains and 55% against not-matched strains. Both live-attenuated and inactivated vaccines showed similar levels of protection against not-matched strains (60% and 55%, respectively). Live-attenuated vaccines performed better than inactivated vaccines in children (80% versus 48%), whereas inactivated vaccines performed better than live-attenuated vaccines in adults (59% versus 39%). There was a large difference (20%) in efficacy against influenza A (69%) and influenza B (49%) types for not-matched strains. Summary estimates of vaccine efficacy were highest when ascertainment was based on culture confirmation.

Conclusion

Influenza vaccines are efficacious, but efficacy estimates depend on many variables including type of vaccine and age of vaccinees, degree of matching of the circulating strains to the vaccine, influenza type, and methods of case ascertainment.     

Determining the effectiveness of the pentavalent rotavirus vaccine against rotavirus hospitalizations and emergency department visits using two study designs

The objective of this study is to determine the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) for preventing rotavirus-related hospitalizations and emergency department (ED) visits during the 2006–07 and 2007–08 rotavirus seasons using two study designs. Active, prospective population-based surveillance was conducted to identify cases of laboratory-confirmed rotavirus-related hospitalizations and ED visits to be used in case-cohort and case-control designs. VE was calculated using one comparison group for the case-cohort method and two comparison groups for the case-control method. The VE estimates produced by the three analyses were similar. Three doses of RV5 were effective for preventing rotavirus-related hospitalizations and ED visits in each analysis, with VE estimated as 92% in all three analyses. Two doses of RV5 were also effective, with VE ranging from 79% to 83%. A single dose was effective in the case-cohort analysis, but was not significant in either of the case-control analyses. The case-cohort and the case-control study designs produced the same VE point estimates for completion of the three dose series. Two and three doses of RV5 were effective in preventing rotavirus-related hospitalizations and ED visits.     

不同类型样本在甲型H1N1流行性感冒诊断及研究中的意义

目的 探讨咽拭子、粪便、血等不同类型标本在甲型H1N1流行性感冒(简称流感)诊断、排毒规律研究中的意义.方法 采集2009年5-6月期间23例甲型H1N1流感确诊患者的135份样本,其中包括13例患者的99份咽拭子、14份粪便、11份血、1份气管抽取物和另10例患者的10份血.分别应用RT-PCR(采用荧光定量PCR方法)、血凝抑制试验检测甲型H1N1流感病毒核酸、血清抗体.结果 13例患者的99份咽拭子中,首次RT-PCR检测阳性的时间为发病后0～7 d,中位数为1 d;咽拭子RT-PCR检测阳性持续时间为1～15 d,中位数为3 d.4例患者呈现间歇排毒现象.1份气管抽取物RT-PCR检测阳性.14份粪便标本中,8份为RT-PCR检测阳性,阳性率为57.14%,RT-PCR检测阳性的时间为发病后1～4 d,中位数为3 d.21份血标本采集时间为发病后2～9 d,RT-PCR检测阳性为1份,采集时间为发病后7 d,阳性率为4.76%.发病后2～9 d采集的21份血标本血清抗体检测结果均为阴性.结论 咽拭子、粪便可用于甲型H1 N1流感患者的早期诊断;咽拭子RT-PCR检测阳性的持续时间比粪便长,且呈现间歇排毒情况.甲型H1N1流感存在少量的病毒血症,早期血标本(发病后9 d内)不能检测到抗体.     

Update: Influenza activity--United States and worldwide, 2006-07 season, and composition of the 2007-08 influenza vaccine

During the 2006-07 season, influenza activity peaked in mid-February in the United States and was associated with less mortality and lower rates of pediatric hospitalizations than during the previous three seasons. In the United States, influenza A (H1) viruses predominated overall, but influenza A (H3) viruses were isolated more frequently than influenza A (H1) viruses late in the season. Although influenza A (H1), A (H3), and B viruses cocirculated worldwide, influenza A (H3) viruses were the most commonly reported type in Europe and Asia. Sporadic cases of avian influenza A (H5N1) virus infections associated with severe illness or death were reported among humans in Cambodia, China, Egypt, Indonesia, Laos, Nigeria, and Viet Nam. This report summarizes influenza activity in the United States and worldwide during the 2006-07 influenza season (October 1, 2006-May 19, 2007) and describes the composition of the 2007-08 influenza vaccine.     

河北省2005—2007年度流感流行特征分析

目的了解河北省流感流行特征、流感病毒优势株的变化，为流感防制提供科学依据。方法通过全国流感监测网络，收集2005—2007年度河北省流感或流感样病例（Influenza Like Illness，ILI）资料，对流行病学，病原学以及流感暴发疫情监测结果进行分析。采集ILI咽拭子标本用MDCK（Madin Darby Canine Kidney）细胞分离病毒，血凝抑制（Hemasslutination Inhibition，HI）试验鉴定病毒型别。结果2005-2007年两个流行期河北省ILI就诊百分比分别为4．50％和3．22％，按月统计ILI就诊百分比高峰出现在2005年12月和2007年1月；2005—2006年流行期采集ILI咽拭子标本938份，分离到流感病毒92株，分离率为9．81％。H1N1亚型57株占61．96％，H3N2亚型6株占6．52％，B型29株占31．52％。2005年11—12月为H1N1亚型；2006年1—2月为H1N1、H3N2亚型和B型同时流行，仍以H1N1亚型为主；进入3月后，H1N1亚型和B型同时流行，但B型已明显上升为优势株。2006—2007年流行期采集标本727份，分离到流感病毒88株，分离率为12．10％，H1N1亚型21株占23．86％，H3N2亚型66株占75．00％，B型1株占1．14％，H3N2亚型毒株为优势株。结论2005—2007年流行期河北省流感流行高峰为当年12月或次年1月。先后出现H1N1、H3N2和B型流感病毒的流行，流感病毒优势株发生了交替变换。     

流行性感冒裂解疫苗安尔来福在婴幼儿及儿童中应用的安全性观察

目的 进一步考察流感裂解疫苗安尔来福在6个月至3岁内婴幼儿及3～11岁儿童中应用的安全性,发现新药临床试验中可能未发现的不良反应.方法 本试验采用开放式临床试验设计,受试者为6个月至3岁以内婴幼儿和3～11岁儿童各100名,婴幼儿组使用剂量为0.25 ml/支,免疫程序为0、28 d.儿童组使用剂量为0.5 ml/支,免疫程序为1针.接种后进行30 min即时反应观察,以及进行24、48、72 h随访观察,接种后第7天如受试者未主动报告任何不良事件,将结束随访观察.结果 接种疫苗后总体不良反应发生率为6.0%(12/200),其中局部不良反应发生率为1.0%(2/200),全身不良反应发生率为5.5%(10/200),幼儿组和儿童组不良反应发生率分别为8.0%(8/100)和4.0%(4/100),均为轻度和中度反应,未见严重不良反应发生.结论 流感裂解疫苗安尔来福在6个月至3岁以内婴幼儿及3～11岁儿童中应用安全性良好.     

用逆转录聚合酶链反应方法检测SARS冠状病毒

目的 应用双位点逆转录聚合酶链反应(RT-PCR)和改良巢式实时RT-PCR方法检测临床标本中SAILS冠状病毒(SAILS-CoV)核酸,以提高检测的可靠性和灵敏度。方法 对2003年杭州市3例严重急性呼吸综合征(SARS)临床确诊患者、4例疑似和27名医学观察者的咽拭子标本用巢式实时RT-PCR检测SAILS-CoV核酸,对阳性扩增产物进行核酸序列测定,同时对3例患者的标本应用半巢式RT-PCR检测另一位点SARS-CoV核酸片段,并应用常规实时RT-PCR技术及改良实时RT-PCR技术进行检测。结果 3例患者的巢式RT-PCR检测结果2例阳性,4例疑似和27名医学观察者均为阴性;阳性扩增产物的核酸序列与SAILS-CoV基因组相应部分序列完全一致。3例患者标本的另一位点的半巢式RT-PCR及实时RT-PCR结果均相同。在检测低拷贝数标本时,常规实时RT-PCR技术在约35个循环后出现弱阳性信号,但改良的巢式实时RT-PCR技术可使强阳性信号在10个扩增循环后出现。结论 双位点RT-PCR方法是提高检测准确性的有效方法,改良巢式实时RT-PCR技术较常规实时RT-PCR技术具有更高的灵敏度。