Effectiveness of 2009 pandemic influenza A(H1N1) vaccines: A systematic review and meta-analysis

BackgroundThe clinical effectiveness of monovalent influenza A(H1N1)pdm09 vaccines has not been comprehensively summarised. We undertook a systematic review and meta-analysis to assess vaccine effectiveness (VE) for adjuvanted and unadjuvanted vaccines.MethodsWe searched healthcare databases and grey literature from 11 June 2009 to 12 November 2014. Two researchers independently assessed titles and abstracts to identify studies for full review. Random effects meta-analyses estimated the pooled effect size of vaccination compared to placebo or no vaccination for crude and adjusted odds ratios (OR) to prevent laboratory confirmed influenza illness (LCI) and related hospitalization. VE was calculated as (1-pooled OR) 1 100. Narrative synthesis was undertaken where meta-analysis was not possible.ResultsWe identified 9229 studies of which 38 at moderate risk of bias met protocol eligibility criteria; 23 were suitable for meta-analysis. Pooled adjusted VE against LCI with adjuvanted and unadjuvanted vaccines both reached statistical significance (adjuvanted: VE = 80%; 95% confidence interval [CI] 59–90%; unadjuvanted: VE = 66%; 95% CI 47–78%); in planned secondary analyses, VE in adults often failed to reach statistical significance and pooled point estimates were lower than observed in children. Overall pooled adjusted VE against hospitalization was 61% (95% CI 14–82%); in planned secondary analyses, adjusted VE attained statistical significance in adults aged 18–64 years and children for adjuvanted vaccines. Adjuvanted vaccines were significantly more effective in children compared to adults for both outcomes.ConclusionsAdjuvanted and unadjuvanted monovalent influenza A(H1N1)pdm09 vaccines were both effective in preventing LCI. Overall, the vaccines were also effective against influenza-related hospitalization. For both outcomes adjuvanted vaccines were more effective in children than in adults.     

The 2009 A (H1N1) influenza virus pandemic: A review

In March and early April 2009 a new swine-origin influenza virus (S-OIV), A (H1N1), emerged in Mexico and the USA. The virus quickly spread worldwide through human-to-human transmission. In view of the number of countries and communities which were reporting human cases, the World Health Organization raised the influenza pandemic alert to the highest level (level 6) on June 11, 2009. The propensity of the virus to primarily affect children, young adults and pregnant women, especially those with an underlying lung or cardiac disease condition, and the substantial increase in rate of hospitalizations, prompted the efforts of the pharmaceutical industry, including new manufacturers from China, Thailand, India and South America, to develop pandemic H1N1 influenza vaccines. All currently registered vaccines were tested for safety and immunogenicity in clinical trials on human volunteers. All were found to be safe and to elicit potentially protective antibody responses after the administration of a single dose of vaccine, including split inactivated vaccines with or without adjuvant, whole-virion vaccines and live-attenuated vaccines. The need for an increased surveillance of influenza virus circulation in swine is outlined.     

The determinants of 2009 pandemic A/H1N1 influenza vaccination: a systematic review

Background

Pandemic A/H1N1 influenza vaccine coverage varied widely across countries. To understand the factors influencing pandemic influenza vaccination and to guide the development of successful vaccination programs for future influenza pandemics, we identified and summarized studies examining the determinants of vaccination during the 2009 influenza pandemic.

Methods

We performed a systematic literature review using the PubMED electronic database from June 2009 to February 2011. We included studies examining an association between a possible predictive variable and actual receipt of the pandemic A/H1N1 influenza vaccine. We excluded studies examining intention or willingness to receive the vaccine.

Results

Twenty-seven studies were identified from twelve countries. Pandemic influenza vaccine coverage varied from 4.8% to 92%. Coverage varied by population sub-group, country, and assessment method used. Most studies used questionnaires to estimate vaccine coverage, however seven (26%) used a vaccination registry. Factors that positively influenced pandemic influenza vaccination were: male sex, younger age, higher education, being a doctor, being in a priority group for which vaccination was recommended, receiving a prior seasonal influenza vaccination, believing the vaccine to be safe and/or effective, and obtaining information from official medical sources.

Conclusions

Vaccine coverage during the pandemic varied widely across countries and population sub-groups. We identified some consistent determinants of this variation that can be targeted to increase vaccination during future influenza pandemics.     

The 2009 influenza A (H1N1) pandemic

Prior to 2009, The Netherlands had prepared itself extensively for a potential pandemic. Multidisciplinary guidelines had been drafted to control transmission and limit adverse outcomes for both a phase of early incidental introduction and for a phase with widespread transmission. The Ministry of Health had ensured a supply and distribution schedule for antivirals and negotiated a contract for vaccine purchases. During the pandemic, existing surveillance was expanded, the established infectious disease response structure was activated, and the previously prepared protocols for communication, diagnostics, use of antivirals, and vaccination implementation were operationalized and implemented. When the pandemic turned out to be less severe than many had anticipated, risk communication and rapid modification of guidelines and communication became a major challenge. Antivirals and pandemic vaccines were reserved for those at high risk for severe outcomes only. Overall, the impact of the pandemic was comparable to the impact of an average seasonal influenza epidemic, but with a shift in (severe) outcomes from the very young and elderly toward young adults. Established prepared protocols enabled timely coordinated responses. In preparing for the worst, sufficient attention must be given to preparing for a mild scenario as well.     

Adult intensive-care patients with 2009 pandemic influenza A(H1N1) infection

In France, the surveillance of hospitalized cases of pandemic influenza was implemented in July 2009 and restricted to intensive-care unit (ICU) patients in November. We described the characteristics of the 1065 adult patients admitted to ICUs and analysed risk factors for severe outcome (mechanical ventilation or death). Eighty-seven percent of cases were aged 15-64 years. The case-fatality ratio was 20%. The risk for severe outcome increased with age and obesity while this association was negative for chronic respiratory disease. Late antiviral therapy was associated with a severe outcome in ICU patients with risk factors (adjusted OR 2·0, 95% CI 1·4-3·0). This study confirms the considerable contribution of young adults to A(H1N1) 2009 mortality. It shows the role of obesity as an independent risk factor for severe disease, and of early antiviral therapy as a protective factor, at least in patients with risk factors.     

Severe illness from 2009 pandemic influenza A (H1N1)--Utah, 2009-10 influenza season

Influenza-associated hospitalizations have been a reportable condition in Utah since 2005, and surveillance for influenza hospitalizations has been a valuable tool for identifying and tracking the population impact of serious influenza illness. During the 2009 influenza A (H1N1) pandemic, Utah public health officials used comparisons with hospitalization data from three previous influenza seasons to rapidly assess the impact of 2009 H1N1 and enable public health authorities to target persons at greatest risk for severe illness. This report summarizes the results of that assessment, which determined that 1,327 2009 H1N1 hospitalizations were reported, compared with an average of 435 seasonal influenza hospitalizations during three previous influenza seasons, and 25.5% of 2009 H1N1 hospitalizations resulted in severe illness (intensive-care unit [ICU] admission or death), compared with 14.0% of seasonal influenza hospitalizations. In addition, 2009 H1N1 disproportionately affected racial/ethnic minorities, pregnant women, and residents of Salt Lake County (the state's most densely populated county). During the 4-month "spring wave" of the H1N1 pandemic, a greater percentage of hospitalizations (30.9%) resulted in severe illness than during the 9-month "fall wave" (23.0%). Surveillance for influenza hospitalizations can provide essential data to public health authorities that will help them identify those populations at greatest risk for severe illness.     

社区甲型流感临床特征分析与比较

目的分析和比较社区散发新型甲型H1N1流感和季节性流感临床特征,为临床诊治甲型流感提供参考依据。方法回顾性分析2009年5-10月来医院发热门诊就诊的具有流感样症状的患者,均经实时荧光定量PCR检测。结果在确诊的129例甲型流感患者中,新型甲型H1N1流感65例,占50.4%,季节性甲型流感64例,占49.6%;新型甲型H1N1流感组平均年龄21岁,季节性甲型流感组36岁,两组差异有统计学意义(P<0.01);新型甲型H1N1流感组学生占47例,占72.3%,季节性甲型流感组13例,占20.3%,两组差异有统计学意义(P<0.01);从临床表现比较,除流涕、扁桃体肿大,两组差异有统计学意义(均P<0.01)外;其他差异均无统计学意义。结论医院确诊的甲型流感患者均为轻型;新型甲型H1N1流感以年轻学生为主;两组甲型流感临床特征相似,需经PCR检测确诊分型。     

北京市2009年甲型H1N1流感疫情分析

目的 分析北京市2009年甲型H1N1流感流行病学特征.方法 采用SPSS11.0软件,对北京市2009年甲型H1N1流感确诊病例的流行病学特征进行描述与分析.结果 2009年北京市共确诊甲型H1N1流感10 802例,重症、危重症病例621例,死亡73例,病死率为0.7%(73/10 802);北京市甲型H1N1流感流行过程可分为输入期、传播期、扩散期、稳中有降期等4个阶段;感染者以青少年为主,占47.9%(5169/10 802),男女性别比为1.3:1;职业分布以学生最多,占52.2%(5 639/10 802),重症、危重症病例及死亡病例均以离退人员为多,分别为15.9%(99/621)及23.3%(17/73);10月份达到流行高峰.结论 北京市2009年甲型H1N1流感病例以青少年学生为主,重症、危重症病例及死亡病例均以离退人员为多.     

2009年广东省甲型H1N1流感流行特征分析

目的分析2009年广东省甲型H1N1流感大流行的流行特征,为采取相应的防控措施提供科学依据。方法收集中国疾病监测信息报告管理系统及广东省流感监测系统的流感样病例监测、病原学监测及暴发疫情监测数据,采用描述性流行病学方法分析2009年广东省甲型H1N1流感的流行特征,并用流感监测数据来估算广东省2009年到医院就诊者中的甲型H1N1流感病例数。结果2009年5月18日广东省报告首例甲型H1N1流感病例,截止2009年12月31日共有21个地级市累计报告甲型H1N1流感确诊病例9 784例,其中重症病例346例,危重病例141例,死亡36例;每周报告甲型H1N1流感病例数占全年病例总数的构成比高峰与流感监测的甲型H1N1流感就诊指数高峰相一致,均出现在2009年11月,并在12月回落,且流感样病例就诊指数也降至警戒线(5%)以下,与季节性流感高峰(7月)完全不同。从病例输入到社区传播可划分为:以国外病例输入为主的输入散发期(5月18日至6月17日);出现聚集性病例,病例主要局限于珠江三角洲的有限传播期(6月18日至7月30日);在全省流感监测网络中连续检出甲型H1N1流感核酸阳性病例为特征的持续传播期(7月31日至8月31日);病例以学校暴发为特征并在全省各市蔓延的广泛传播期(9月1日至12月31日)。分析834例临床资料完整的病例的临床表现主要以发热(95.56%)、咳嗽(59.11%)、咽痛(42.45%)等呼吸道症状为主。估算广东省2009年到医院就诊者中甲型H1N1流感感染数不少于270万例。结论广东省2009年甲型H1N1流感流行高峰出现在11月份,为单月高峰,多数病例临床表现温和,推算在全人群中感染率尚在低水平。     

Outbreaks of pandemic (H1N1) 2009 and seasonal influenza A (H3N2) on cruise ship

To determine the extent and pattern of influenza transmission and effectiveness of containment measures, we investigated dual outbreaks of pandemic (H1N1) 2009 and influenza A (H3N2) that had occurred on a cruise ship in May 2009. Of 1,970 passengers and 734 crew members, 82 (3.0%) were infected with pandemic (H1N1) 2009 virus, 98 (3.6%) with influenza A (H3N2) virus, and 2 (0.1%) with both. Among 45 children who visited the ship's childcare center, infection rate for pandemic (H1N1) 2009 was higher than that for influenza A (H3N2) viruses. Disembarked passengers reported a high level of compliance with isolation and quarantine recommendations. We found 4 subsequent cases epidemiologically linked to passengers but no evidence of sustained transmission to the community or passengers on the next cruise. Among this population of generally healthy passengers, children seemed more susceptible to pandemic (H1N1) 2009 than to influenza (H3N2) viruses. Intensive disease control measures successfully contained these outbreaks.     

Household transmission of Pandemic (H1N1) 2009 Virus, Taiwan

During August-November 2009, to investigate disease transmission within households in Taiwan, we recruited 87 pandemic (H1N1) 2009 patients and their household members. Overall, pandemic (H1N1) 2009 virus was transmitted to 60 (27%) of 223 household contacts. Transmission was 4× higher to children than to adults (61% vs. 15%; p<0.001).