Seroepidemiologic Effects of Influenza A(H1N1)pdm09 in Australia,New Zealand,and Singapore

To estimate population attack rates of influenza A(H1N1)pdm2009 in the Southern Hemisphere during June–August 2009, we conducted several serologic studies. We pooled individual-level data from studies using hemagglutination inhibition assays performed in Australia, New Zealand, and Singapore. We determined seropositive proportions (titer >40) for each study region by age-group and sex in pre- and postpandemic phases, as defined by jurisdictional notification data. After exclusions, the pooled database consisted of, 4,414 prepandemic assays and 7,715 postpandemic assays. In the prepandemic phase, older age groups showed greater seropositive proportions, with age-standardized, community-based proportions ranging from 3.5% in Singapore to 11.9% in New Zealand. In the postpandemic phase, seropositive proportions ranged from 17.5% in Singapore to 30.8% in New Zealand, with highest proportions seen in school-aged children. Pregnancy and residential care were associated with lower postpandemic seropositivity, whereas Aboriginal and Torres Strait Islander Australians and Pacific Peoples of New Zealand had greater postpandemic seropositivity.     

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).     

某警队1起甲型H1N1流感暴发调查

目的调查2009-10某警队1起甲型H1N1流感暴发的疫情规模、传染来源及传播途径。方法制定病例定义,开展病例主动搜索和病例对照研究。结果首发病例为另1起确诊甲流疫情的密切接触者,归队后发病,之后陆续57人发病,罹患率20%。病例集中在新警大队,在各中队、班和楼层的分布差异均无统计学意义,但存在宿舍聚集性。病例和对照中吸烟、洗手、看电视、用电脑的情况差异无统计学意义,但吸烟者患病的相对危险度为不吸烟的4.25倍。结论本起疫情为1起输入性病例引起的甲型H1N1流感暴发,因警员围坐吸烟行为引起病毒的传播。防止飞沫传播在流感大流行中具有重要意义。     

Differential effects of pandemic (H1N1) 2009 on remote and indigenous groups, Northern Territory, Australia, 2009

Pandemic (H1N1) 2009 influenza spread through the Northern Territory, Australia, during June-August 2009. We performed 2 cross-sectional serologic surveys on specimens from Northern Territory residents, with 445 specimens obtained prepandemic and 1,689 specimens postpandemic. Antibody titers were determined by hemagglutination inhibition against reference virus A/California/7/2009 on serum samples collected opportunistically from outpatients. All specimens had data for patients' gender, age, and address, with patients' indigenous status determined for 94.1%. Protective immunity (titer >40) was present in 7.6% (95% confidence interval [CI] 5.2%-10.1%) of prepandemic specimens and 19.5% (95% CI 17.6%-21.4%) of postpandemic specimens, giving a population-standardized attack rate of 14.9% (95% CI 11.0%-18.9%). Prepandemic proportion of immune persons was greater with increasing age but did not differ by other demographic characteristics. Postpandemic proportion of immune persons was greater in younger groups and around double in indigenous persons. Postpandemic proportion immune was geographically heterogeneous, particularly among remote-living and indigenous groups.     

An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers

Mass vaccination was the most effective prophylaxis for protecting the population during the influenza H1N1 pandemic. We have evaluated the tolerability, immunogenicity and kinetics of the antibody response to a monovalent oil-in-water (AS03) adjuvanted human pandemic split influenza A/California/7/2009 H1N1 (3.75 μg haemagglutinin) vaccine in health care workers. Vaccination elicited a rapid and early protective level of haemagglutination inhibition antibody from 6 to 7 days post vaccination, and by 14 to 21 days post vaccination, up to 98% of vaccinees had protective antibody titres which persisted for at least 3 months in 84-92% of subjects. A rapid induction of protective antibody is important in reducing community spread of pandemic influenza and in helping maintain the integrity of the health care system during the pandemic.     

Lessons from pandemic influenza A(H1N1): the research-based vaccine industry's perspective

As A(H1N1) influenza enters the post-pandemic phase, health authorities around the world are reviewing the response to the pandemic. To ensure this process enhances future preparations, it is essential that perspectives are included from all relevant stakeholders, including vaccine manufacturers. This paper outlines the contribution of R&D-based influenza vaccine producers to the pandemic response, and explores lessons that can be learned to improve future preparedness.The emergence of 2009 A(H1N1) influenza led to unprecedented collaboration between global health authorities, scientists and manufacturers, resulting in the most comprehensive pandemic response ever undertaken, with a number of vaccines approved for use three months after the pandemic declaration. This response was only possible because of the extensive preparations undertaken during the last decade.During this period, manufacturers greatly increased influenza vaccine production capacity, and estimates suggest a further doubling of capacity by 2014. Producers also introduced cell-culture technology, while adjuvant and whole virion technologies significantly reduced pandemic vaccine antigen content. This substantially increased pandemic vaccine production capacity, which in July 2009 WHO estimated reached 4.9 billion doses per annum. Manufacturers also worked with health authorities to establish risk management plans for robust vaccine surveillance during the pandemic. Individual producers pledged significant donations of vaccine doses and tiered-pricing approaches for developing country supply.Based on the pandemic experience, a number of improvements would strengthen future preparedness. Technical improvements to rapidly select optimal vaccine viruses, and processes to speed up vaccine standardization, could accelerate and extend vaccine availability. Establishing vaccine supply agreements beforehand would avoid the need for complex discussions during a period of intense time pressure.Enhancing international regulatory co-operation and mutual recognition of approvals could accelerate vaccine supply, while maintaining safety standards. Strengthening communications with the public and healthcare workers using new approaches and new channels could help improve vaccine uptake. Finally, increasing seasonal vaccine coverage will be particularly important to extend and sustain pandemic vaccine production capacity.     

2009-2010 seasonal and pandemic A (H1N1) influenza vaccination among healthcare workers

Influenza vaccination recommendations are traditionally met with low compliance by healthcare workers (HCWs). The aim of this study is to analyze influenza vaccination among HCWs following a vaccination strategy characterized by an increased effort to maximize the hospital vaccination rate. For this, 2009-2010 seasonal and pandemic influenza vaccination rates among 2739 HCWs at a tertiary university hospital were evaluated. The seasonal influenza vaccination rate was 26.7% (48.3% increase vs. 2008-2009, p = 0.0000), and 14.8% in the case of pandemic influenza. HCWs with direct patient contact showed similar seasonal (25.7%) and pandemic (15.4%) influenza vaccination rates compared to the overall rates. Physician vaccination displayed the highest rate, showing significant differences vs. total rate (38.3%, p = 0.0007 for seasonal, and 32.2%, p = 0.0000 for pandemic influenza). The areas in which the vaccination strategy was most active reflected a significant increase (32.6%, p = 0.0056 for seasonal, and 25.2%, p = 0.0000 for pandemic influenza). It therefore appears that more active campaigns might increase influenza vaccination among HCWs.     

Emergency department visits for influenza A(H1N1)pdm09, Davidson County, Tennessee, USA

To determine the number of emergency department visits attributable to influenza A(H1N1)pdm09 in Davidson County, Tennessee, USA, we used active, population-based surveillance and laboratory-confirmed influenza data. We estimated ≈10 visits per 1,000 residents during the pandemic period. This estimate should help emergency departments prepare for future pandemics.     

Excess influenza hospital admissions and costs due to the 2009 H1N1 pandemic in England

Influenza pandemics considerably burden affected health systems due to surges in inpatient admissions and associated costs. Previous studies underestimate or overestimate 2009/2010 influenza A/H1N1 pandemic hospital admissions and costs. We robustly estimate overall and age‐specific weekly H1N1 admissions and costs between June 2009 and March 2011 across 170 English hospitals. We calculate H1N1 admissions and costs as the difference between our administrative data of all influenza‐like‐illness patients (seasonal and pandemic alike) and a counterfactual of expected weekly seasonal influenza admissions and costs established using time‐series models on prepandemic (2004–2008) data. We find two waves of H1N1 admissions: one pandemic wave (June 2009–March 2010) with 10,348 admissions costing £20.5 million and one postpandemic wave (November 2010–March 2011) with 11,775 admissions costing £24.8 million. Patients aged 0–4 years old have the highest H1N1 admission rate, and 25‐ to 44‐ and 65+‐year‐olds have the highest costs. Our estimates are up to 4.3 times higher than previous reports, suggesting that the pandemic's burden on hospitals was formerly underassessed. Our findings can help hospitals manage unexpected surges in admissions and resource use due to pandemics.     

北京市2009年甲型H 1N 1流感防控效果定量评价

目的 定量评价北京市甲型H1N1流感的防控措施效果,为制定和调整传染病防控策略提供依据.方法 利用北京市2009年甲型H1N1流感流行病学数据,基于传染病传播动力学机制,考虑了甲型H1N1流感的季节性,并引入疫苗接种量,建立定量评价甲型H1N1流感防控效果的数学模型.结果 2009年北京市甲型H1N1流感的平均潜伏期约为1.82 d,平均感染期约为2.08 d, 前中后三期有效再生数分别为1.13、1.65 和 0.96;北京市采取了一系列甲型H1N1 流感防控措施使2009年甲型H1N1流感报告的实际病例数远远小于其自然状态下的累计例数;接种甲型H1N1流感疫苗使2009年累计病例数减少24.08%,且使发病高峰时间推后.结论 北京市采取的一系甲型H1N1流感防控措施整体上显著有效,接种甲型H1N1流感疫苗不仅降低了疫情规模, 还能延迟疫情达到高峰的时间 .     

Pandemic influenza A/H1N1 vaccine administered sequentially or simultaneously with seasonal influenza vaccine to HIV-infected children and adolescents

In order to evaluate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to HIV-infected children and adolescents, 36 HIV-infected children and adolescents, and 36 age- and gender-matched healthy controls were randomised 1:1 to receive the pandemic vaccine upon enrolment and the seasonal vaccine one month later, or to receive the pandemic and seasonal vaccines simultaneously upon enrolment. Seroconversion and seroprotection rates against the pandemic influenza A/H1N1 virus were 100% two months after vaccine administration in both groups, regardless of the sequence of administration. Geometric mean titres against pandemic and seasonal antigens were significantly higher when the seasonal and pandemic vaccines were administered simultaneously than when the seasonal vaccine was administered alone. Local and systemic reactions were mild and not increased by simultaneous administration. In conclusion, the 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine is as immunogenic, safe and well tolerated in HIV-infected children and adolescents as in healthy controls. Its simultaneous administration with virosomal-adjuvanted seasonal antigens seems to increase immune response to both pandemic and seasonal viruses with the same safety profile as that of the pandemic vaccine alone. However, because this finding cannot be clearly explained by an immunological viewpoint, further studies are needed to clarify the reasons of its occurrence.     

2010年兵团甲型H1N1流感血清学检测结果分析

目的:了解兵团2010年自然人群新甲型H1N1流感抗体水平及流行趋势。方法:利用血凝抑制(HI)试验方法检测兵团不同时间、人群新甲型H1N1流感抗体,比较不同时间、人群的新甲型H1N1流感抗体阳性率。结果:从1月-3月不同时间的检测,甲型H1N1流感抗体阳性率随着时间推移总体呈现下降趋势,依次为16.7%、15.6%、5.0和4.6%,差别有统计学意义。不同年龄组人群的甲型H1N1抗体阳性率差别较大,7岁～17岁年龄组最高(35.0%),不同年龄组抗体阳性率(P)差别有统计学意义。不同年龄组人群接种甲型H1N1疫苗后抗体阳性率差别无统计学意义。结论:兵团有10.2%的人群具有甲型H1N1流感保护性抗体,普通人群中已经建立一定的免疫屏障。7岁～17岁人群是新甲型H1N1流感暴发的主要人群,应重点防控。     

Adverse events following pandemic influenza A (H1N1) 2009 monovalent and seasonal influenza vaccinations during the 2009–2010 season in the active component U.S. military and civilians aged 17–44 years reported to the Vaccine Adverse Event Reporting System

BackgroundNo comparative review of Vaccine Adverse Event Reporting System (VAERS) submissions following pandemic influenza A (H1N1) 2009 and seasonal influenza vaccinations during the pandemic season among U.S. military personnel has been published.MethodsWe compared military vs. civilian adverse event reporting rates. Adverse events (AEs) following vaccination were identified from VAERS for adults aged 17–44 years after pandemic (monovalent influenza [MIV], and seasonal (trivalent inactivated influenza [IIV3], live attenuated influenza [LAIV3]) vaccines. Military vaccination coverage was provided by the Department of Defense’s Defense Medical Surveillance System. Civilian vaccination coverage was estimated using data from the National 2009 H1N1 Flu Survey and the Behavioral Risk Factor Surveillance System survey.ResultsVaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain–Barré Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million).ConclusionsDespite higher vaccination coverage in service personnel, the rate of serious AEs following MIV was about half that in civilians. The rate of GBS reported following MIV was higher in the military.     

江苏省2009年3岁以上自然人群新甲型H1N1流感血清流行病学调查

目的 了解江苏省2009年3岁以上自然人群新甲型H1N1流感抗体水平及流行趋势.方法 利用微量半加敏血凝抑制(HI)方法检测江苏省不同时间(2008年11月和2009年7、8、11月)人群新甲型H1N1流感抗体,比较不同时间、人群及地区的新甲型H1N1流感保护性抗体阳性率和抗体几何平均滴度(GMTs).结果 在新甲型H1N1流感输入江苏地区后第一个流行季节内,2009年7、8、11月人群HI保护性抗体阳性率依次为3.46%、7.59%和16.94%,表现出随时间推移而呈总体增长趋势(P=0.000),不同时间点的性别间保护性抗体阳性率的差异无统计学意义(P＞0.05);除2009年11月外,不同性别间的抗体GMT差异均无统计学意义.同一时间点不同年龄组间、同一年龄组的不同时间点间,HI保护性抗体阳性率、抗体GMT水平比较的差异均有统计学意义(P＜0.05).HI保护性抗体阳性率和抗体GMT存在地区差异(P＜0.05).结论 在2009年8月后江苏地区12～17岁人群成为新甲型H1N1流感暴发的主要人群,至2009年11月该人群总体新甲型H1N1流感保护性抗体阳性率仍较低,该病在全省的流行仍将持续一段时间.     

Oseltamivir-resistant pandemic (H1N1) 2009 virus infection in England and Scotland, 2009-2010

Oseltamivir has been widely used for pandemic (H1N1) 2009 virus infection, and by April 30, 2010, a total of 285 resistant cases were reported worldwide, including 45 in the United Kingdom. To determine risk factors for emergence of oseltamivir resistance and severe infection, a case-control study was conducted in the United Kingdom. Study participants were hospitalized in England or Scotland during January 4, 2009-April 30, 2010. Controls had confirmed oseltamivir-sensitive pandemic (H1N1) 2009 virus infections, and case-patients had confirmed oseltamivir-resistant infections. Of 28 case-patients with available information, 21 (75%) were immunocompromised; 31 of 33 case-patients (94%) received antiviral drugs before a sample was obtained. After adjusting for confounders, case-patients remained significantly more likely than controls to be immunocompromised and at higher risk for showing development of respiratory complications. Selective drug pressure likely explains the development of oseltamivir resistance, especially among immunocompromised patients. Monitoring of antiviral resistance is strongly recommended in this group.     

2010年四川省甲型H1N1流感血清学调查

目的了解四川省人群甲型H1N1流感病毒抗体水平,为及时科学评估疫情发展趋势和完善防控策略与措施提供依据。方法按照国家方案采集不同年龄组人群血清标本,用血凝抑制(HI)试验方法进行抗体检测,HI抗体滴度≥1∶40判为阳性。结果四川省甲型H1N1流感阳性率17.39%(663/3 812);不同地区阳性率差异无统计学意义;6～17岁组阳性率最高(20.52%);男女性阳性率差异无统计学意义;就诊人群阳性率高于献血人群和体检人群,差异有统计学意义。结论四川省人群甲型H1N1流感阳性率较低,,甲型H1N1流感在人群中的自然感染未形成有效免疫屏障,甲型H1N1流感疫苗接种仍有必要。     

Use of antiviral drugs to reduce household transmission of pandemic (H1N1) 2009, United Kingdom

The United Kingdom implemented a containment strategy for pandemic (H1N1) 2009 through administering antiviral agents (AVs) to patients and their close contacts. This observational household cohort study describes the effect of AVs on household transmission. We followed 285 confirmed primary cases in 259 households with 761 contacts. At 2 weeks, the confirmed secondary attack rate (SAR) was 8.1% (62/761) and significantly higher in persons <16 years of age than in those >50 years of age (18.9% vs. 1.2%, p<0.001). Early (<48 hours) treatment of primary case-patients reduced SAR (4.5% vs. 10.6%, p = 0.003). The SAR in child contacts was 33.3% (10/30) when the primary contact was a woman and 2.9% (1/34) when the primary contact was a man (p = 0.010). Of 53 confirmed secondary case-patients, 45 had not received AV prophylaxis. The effectiveness of AV prophylaxis in preventing infection was 92%.     

Protection induced by early stage vaccination with pandemic influenza virus-like particles

The 2009 worldwide influenza pandemic emphasized the need for new approaches to develop emergency vaccines. In this study, a virus-like particle vaccine comprised of hemagglutinin (HA) and M1 from the pandemic influenza virus A/California/04/09 were used and its ability to induce protective immunity during the early stage of vaccination was assessed in a mouse model. A single intramuscular vaccination with virus-like particles (VLPs) provided protection on days 4 and 7 post-vaccination against lethal virus challenge with only moderate body weight loss. VLP vaccination induced significantly higher IgG antibody responses and high hemagglutinin inhibition (HAI) titers on day 4 post-vaccination. A predominant IgG2a antibody response and viral neutralizing antibodies were induced on day 7. These immune responses were closely correlated with protection. Lung virus titers decreased significantly on day 7 compared to those on day 4 post-vaccination. The lung virus titer on day 4 post-vaccination also decreased significantly compared to that of the naïve control. These results demonstrate that VLP vaccination confers effective protection during the early stage after vaccination in a mouse model.     

Comparison of Pandemic (H1N1) 2009 and Seasonal Influenza, Western Australia, 2009

We compared confirmed pandemic (H1N1) 2009 influenza and seasonal influenza diagnosed in Western Australia during the 2009 influenza season. From 3,178 eligible reports, 984 pandemic and 356 seasonal influenza patients were selected; 871 (88.5%) and 288 (80.9%) were interviewed, respectively. Patients in both groups reported a median of 6 of 11 symptoms; the difference between groups in the proportion reporting any given symptom was <10%. Fewer than half the patients in both groups had >1 underlying condition, and only diabetes was associated with pandemic (H1N1) 2009 influenza (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1–3.5). A total of 129 (14.8%) persons with pandemic (H1N1) 2009 and 36 (12.5%) persons with seasonal influenza were hospitalized (p = 0.22). After controlling for age, we found that patient hospitalization was associated with pandemic (H1N1) 2009 influenza (OR 1.5; 95% CI 1.1–2.1). Contemporaneous pandemic and seasonal influenza infections were substantially similar in terms of patients’ symptoms, risk factors, and proportion hospitalized.     

Improved neutralizing antibody response in the second season after a single dose of pandemic (H1N1) 2009 influenza vaccine in HIV-1-positive adults

Neutralizing antibody titers were determined before and after a single dose of pandemic (H1N1) 2009 influenza vaccine in HIV-1-positive Japanese adults in the first season of the pandemic and in those in the second season who had already received the vaccine in the first season. The antibody response rate at 2-month post-vaccination increased significantly from 49.0% (50/102, 95%CI: 39.0-59.1%) in the 2009/2010 season to 66.7% (42/63, 95%CI: 53.7-78.1%) in the 2010/2011 season. Geometric mean antibody titers (fold dilution) at baseline, at 2 months, and at 4 months also increased significantly from 4.4 (95%CI: 3.3-5.7), 19.0 (95%CI: 13.4-26.8) and 13.7 (95%CI: 9.3-20.2), respectively, in the 2009/2010 season to 8.3 (95%CI: 5.8-11.7), 47.0 (95%CI: 32.2-68.6) and 38.2 (95%CI: 23.8-61.4), respectively, in the 2010/2011 season. Although the vaccine response was low in the first season, it was improved in the second season.