A(H1N1)v2009: a controlled observational prospective cohort study on vaccine safety in pregnancy

Background

A(H1N1)v2009 influenza vaccination of pregnant women was a challenge for health care providers, as little safety data were available.

Methods

We prospectively followed the pregnancies of women who were vaccinated at any time during pregnancy or ≤4 weeks prior to conception and compared these outcomes to a control cohort matched by the estimated date of birth. Primary endpoints: rate of spontaneous abortion and major malformations. Secondary endpoints: preeclampsia, gestational age at birth, and birth weight.

Results

Pregnancy outcome of 323 women immunized with adjuvanted or non-adjuvanted A(H1N1)v2009 influenza vaccines from 2009-09-28 to 2010-03-31 were compared to 1329 control subjects. The risk for spontaneous abortions (HR 0.89; 95% CI 0.36–2.19) and the rate of major malformations (all trimesters: OR 0.87; 95% CI 0.38–1.77; preconception and first trimester exposure: OR 0.79; 95% CI 0.13–2.64) did not vary between the two cohorts. Furthermore, there was no increase in preeclampsia, prematurity, and intrauterine growth retardation in the vaccinated cohort.

Conclusion

The results of our study do not indicate a risk for the pregnant woman and the developing embryo/fetus after H1N1 vaccination. We provide and apply methods novel in observational studies on pregnancy outcome, especially if a single dose exposure is investigated.     

妊娠合并重症新型甲型H1N1流感患者抗H1N1抗体IgG亚类的分布

目的探讨妊娠合并重症甲型H1N1流感患者抗H1N1抗体各IgG亚类在血清中的分布特点。方法收集2009年11月14日-12月31日,确诊的女性甲型H1N1流感患者,分为妊娠病例组,非妊娠病例组,同时收集抗甲型H1N1抗体阳性的健康妊娠女性作为妊娠对照组,采用ELISA法检测各组血清特异性IgG及亚类的百分结合率。结果妊娠病例组的IgG2I、gG3I、gG4亚类的百分结合率中位数分别为53.0%、65.0%、61.6%,均低于妊娠对照组,差异有统计学意义(P<0.05);各组的特异性抗甲型H1N1 IgG均以IgG1亚类为主,为>70.0%,妊娠病例组的IgG2亚类占5.0%,低于非妊娠病例组的10.0%和妊娠对照组的8.0%,(P<0.05)。结论妊娠合并甲型H1N1流感患者中,特异性抗甲型H1N1 IgG以IgG1亚类为主,IgG2亚类的绝对及相对下降与甲型H1N1感染相关。     

Determinants of A (H1N1) vaccination: cross-sectional study in a population of pregnant women in Quebec

Background

Because of the risk of complication, pregnant women were a priority target for vaccination during the A (H1N1) pandemic influenza. In Quebec, 63% of pregnant women were vaccinated, which is a higher rate than vaccination against seasonal influenza. However, the behaviour of pregnant women relative to the vaccination during the H1N1 pandemic is unknown. The present study was aimed at identifying factors influencing the decision-making of pregnant women regarding H1N1 vaccination.

Methods

A cross-sectional survey was conducted in February 2010 in pregnant women or in early postpartum at the Sherbrooke University Hospital Centre using a self-administered questionnaire based on the Health Belief Model (HBM). Data items collected were: socio-demographic data, vaccination status, information sources consulted, knowledge on vaccination, and the HBM dimensions: effectiveness and risks of vaccination, severity and vulnerability towards the influenza. The associations between questionnaire variables and vaccination status were assessed by univariate and multivariate analysis.

Results

Of the 250 women interviewed, 95% knew that the vaccination was recommended, but only 76% received the vaccine. Variables positively associated with vaccination were late vaccination during pregnancy (OR = 7.3, 95% CI 2.1-25.3), belief in the efficacy of the vaccine (OR = 7, 95% CI 2-23.4), and consultation of the Pandémie-Québec website (OR = 4.5, 95% CI 1.5-13.4). However, the belief that the vaccine had not been adequately tested (OR = 0.08, 95% CI 0.02-0.35) and consultation of mainstream websites (OR = 0.22, 95% CI 0.06-0.81) were associated with lower vaccination rates.

Conclusions

The vast majority of pregnant women were aware of the recommendations relative to A (H1N1) vaccination. Internet media played an important role in their decision to get vaccinated. Better information on the safety of the vaccine must be prepared for future pandemics.     

Acceptance of vaccination during pregnancy: experience with 2009 influenza A (H1N1) in the Netherlands

Objectives

In 2009, the Dutch government advised pregnant women to get vaccinated against influenza A (H1N1). A study was set up to gain insight into vaccination coverage and reasons why pregnant women seek vaccination or not.

Methods

We invited 14,529 pregnant women to complete an internet survey on vaccination during pregnancy in general and against 2009 influenza A (H1N1). Differences in background characteristics between unvaccinated and vaccinated women were investigated. Prediction analyses were carried out to determine which survey statement had the greatest impact on vaccination status or intention to get vaccinated during pregnancy.

Results

Of the 2993 included respondents, 63% reported to be vaccinated against 2009 influenza A (H1N1). Vaccination coverage was higher among older birth cohorts, women who had been pregnant before, women with underlying medical conditions, and women who reported no defined ‘life philosophy’. Protection of the child (after birth), the government's advice and possible harmful effects of the vaccine for the unborn child had the greatest predictive value for vaccination status. With regards vaccination during future pregnancies, 39% had a positive intention to obtain vaccination and 45% were neutral. The government's advice was the strongest predictor for intention. Furthermore, women expressed concern over lack of sufficient knowledge about vaccine safety.

Conclusions

A considerable number of pregnant women in the Netherlands reported to be vaccinated against 2009 influenza A (H1N1). The challenge for the government in the future will be to provide pregnant women and health care professionals with sufficient and clear information about disease severity and the benefits and safety of vaccination.     

无锡市甲型H1N1流感及季节性流感疫苗接种效果分析

目的调查流感样病例(ILI)和无锡市一般人群中甲型H1N1流感疫苗及季节性流感疫苗的接种情况,评估疫苗接种后对人群的保护效果。方法以无锡市2家哨点医院为基础,采集流感样病例病毒核酸检测阳性的病例作为病例组,共1 529人,同时按照"病例"的电话信息,随机产生电话号码选择、年龄匹配的一般人群作为对照组,共380人。结果病例组甲型H1N1流感疫苗接种率为6.1%(94/1 529),对照组甲型H1N1流感疫苗接种率为12.1%(46/380),两组比较,差异有统计学意义(P0.01);甲型H1N1流感病例中接种甲型H1N1流感疫苗的比例为12.5%(3/24),门诊检测阴性的ILI病例接种甲型H1N1流感疫苗的比例为6.1%(78/1 273),"接种甲型H1N1流感疫苗"因素的OR值为0.457(P=0.201);以电话调查一般人群(330例)作为对照组,接种甲型H1N1流感疫苗的比例为13.3%(44/330),OR值为1.077(P=0.908)。结论该次调查说明接种甲型H1N1流感疫苗对预防流感样病例有一定效果,但由于样本量较少,24种方法病例对照分析均未得出差异有统计学意义。     

Delayed focal lipoatrophy after AS03-adjuvanted influenza A (H1N1) 2009 vaccine

Intramuscular vaccination may lead to loss of subcutaneous fat resulting in skin depression at the site of injection. We report for the first time a delayed lipoatrophy after with AS03-adjuvanted influenza A (H1N1) 2009 vaccine. Inadequate administration into the adipose tissue may be causative. During next pandemic, education to optimal intramuscular administration and prolonged monitoring of adverse effects could be proposed.     

11例甲型H1N1流感孕产妇的临床分析

目的 探索孕产妇合并重型甲型H1N1流感的临床特点、诊治经验及对新生儿的影响.方法 对我院2009年11-12月收治的11例重型甲型H1N1流感孕产妇患者(危重症3例)的临床资料进行回顾性分析.结果 11例患者均存在发热咳嗽症状,体温38.7～39.6℃,持续3～14 d.淋巴细胞降低9例,中性粒细胞比例增高9例,C反应蛋白均增高(12～129 mg/L),低蛋白血症者9例(22.4～30.2 mg/L).11例胸部影像学均提示两肺广泛片状密度增高,经神经氨酸酶抑制剂抗病毒、抗细菌感染和(或)综合治疗,10例痊愈、1例好转出院,9例孕妇患者均继续妊娠.仅1例新生儿败血症经治疗已痊愈,余新生儿及胎儿情况良好.结论 孕产妇感染甲型H1N1流感易发展为重症,及时抗病毒抗菌、辅助支持治疗很重要,继续妊娠多数是安全的,但对新生儿的影响还有待进一步探讨.     

甲型H1N1流感疫苗接种对其暴发疫情的影响

目的了解甲型H1N1流感(甲流)疫苗接种后对甲流暴发疫情的影响。方法对2011年4—5月发生在学校的1起甲流暴发疫情进行流行病学描述性分析,用回顾性队列研究的方法分析甲流疫苗接种对该起暴发疫情的影响。结果该校542名师生中191人患病,罹患率为35.24%,发病时间主要集中在4月19—25日,发病人群主要为1～6年级的小学生(χ2=9.972,P0.01),住校生发病高于非住校生,112名接种过甲流疫苗的师生发病率为16.96%,明显低于未接种疫苗的师生(40%),差异有统计学意义(χ2=20.661,P0.05),OR=0.306(95%CI∶0.180～0.521)。结论接种甲流疫苗可以有效预防甲型H1N1流感的发生,减少暴发疫情的发病率。     

江苏省甲型H1N1流感裂解疫苗的免疫效果分析

2009年甲型H1N1流感的流行引起了广泛重视,接种疫苗是预防流感流行、降低死亡率和病死率的最有效方法[1],本研究通过比较不同人群甲型H1N1抗体水平变化趋势,初步评估甲型H1N1流感裂解疫苗的免疫效果. 1.对象与方法: (1)研究对象:2009年11月、12月、2010年2月,在江苏省随机选择甲型H1N1流感疫苗接种人群(免疫人群),连续采集同一批人群(共281人)免疫前、免疫后1个月及3个月的血清标本(排除季节性流感疫苗接种者和接种前1个月内有流感样症状者);连续采集甲型H1N1流感确诊病例(发病时间为2009年10月15日至11月15日,经RT-PCR检测确诊为甲型H1N1流感病毒感染[1])同一组病例发病2周内(107例)、发病后1个月(77例)及3个月(52例)的血清标本(排除甲型H1N1流感疫苗和季节性流感疫苗接种者),选择同时期自然人群作为背景资料.     

2009～2010年北京市孕妇甲型H1N1流感流行病学特征

目的分析2009～2010年甲型H1N1流感大流行期间,孕妇甲型H1N1流感确诊病例流行病学特征。方法对北京市孕妇甲型H1N1流感确诊病例开展流行病学调查,描述病例发病时间、地区和职业分布,并利用Logistic回归探讨导致孕妇甲型H1N1流感病例死亡的相关因素。结果 2009～2010年北京市孕妇中累计出现确诊病例81例,危重症病例占30.9%,确诊病例病死率6.2%,死亡病例均为外来务工人员。孕妇危重症病例所占构成比和病例病死率高于育龄期女性(χ2=88.2,P<0.001;χ2=9.6,P<0.005)。多因素logistic回归分析显示,发病治疗时间间隔长、体重指数高是导致孕妇甲型H1N1流感病例死亡的危险因素。结论孕妇甲型H1N1流感确诊病例易并发呼吸衰竭和感染中毒性休克,且出现危重病例和死亡病例的危险性高于育龄期女性,外来务工人员是孕妇甲型H1N1流感防控的高危人群。     

孕妇甲型H1N1流感的影像学表现

目的 研究孕妇甲型H1N1流感影像特点.方法 回顾性分析经临床诊断证实的14例甲型H1N1流感孕妇的资料,所有病例均行胸部X线片及CT影像学检查,实验室检查.结果 所有病例在出现临床症状后胸部影像学检查均有异常表现,轻症患者8例,其中6例为单个肺叶磨玻璃密度及片状高密度,2例双肺下叶片状高密度,3例伴少量胸腔积液;重症患者6例,表现为双肺多叶受累团絮状高密度,同时伴有胸腔积液及心包积液.结论 甲型H1N1流感孕妇患者影像学征像为非特异性急性感染性病变,有一定特征性,影像学检查有助于其早期诊断及鉴别诊断.     

人口流动强度与甲型H1N1流感和人感染H7N9禽流感流行的相关性研究

目的 探讨人口流动强度与甲型H1N1流感（简称H1N1）和人感染H7N9禽流感（简称H7N9）的流行关系的模式。方法 利用2009年H1N1监测数据和2013年至2017年2月的H7N9监测数据,采用秩相关、主成分分析、Getis-Ord Gi*热点分析和对应分析探讨人口流动强度与上述两种传染病流行的相关关系。结果 人口流动强度与H1N1和H7N9的发病数均呈正相关。家禽出栏量与H7N9的发病数和人口流动强度也呈正相关。人口流动强度分别与H1N1（〖XC小五号.EPS;P〗=43.40,P<0.0001）和H7N9（〖XC小五号.EPS;P〗=51.82,P=0.0010）的热区位于对应分析图的相同区域,且均存在相同级别的热区聚集在一起,提示人口流动强度与这两种疾病均存在一定的对应关系;家禽出栏量和H7N9的热区位于对应分析图的相同区域,且热区级别大致一一对应,即存在相对严格的对应关系（〖XC小五号.EPS;P〗=36.47,P=0.0140）。人口流动强度与家禽出栏量也存在一定的对应关系,两者的热区位于对应分析图的同一区域（〖XC小五号.EPS;P〗=32.26,P=0.0410）。结论 人口流动强度与H1N1的暴发流行有相关关系,而人口流动强度与H7N9的流行关系是一种典型的“人-物流”的动物源性的传染病模式。     

广州市甲型H1N1流感裂解疫苗人群免疫效果观察

为有效应对甲型H1N1流感疫情,评价疫苗的人群应用效果,本研究选取广州市自愿接种甲型H1N1流感疫苗的健康成年人,分别检测免前和免后第15天、第30天血清抗体滴度水平,对甲型H1N1流感裂解疫苗的人群免疫效果进行了观察.     

2009年新型甲型H1N1流感不同剂型疫苗免疫效果Meta分析

为有效控制甲型H1N1流感疫情,接种疫苗是当前最为经济、科学的手段.当前已有研究报道了前期甲型H1N1流感疫苗人群免疫效果和安全性评估的研究情况,WHO也肯定了其效果.但目前对于不同剂型疫苗免疫效果结论不尽一致,缺乏全面、系统的权威报道.为此,本研究对国内外报道的不同剂型新型甲型H1N1流感疫苗免疫效果进行Meta分析,以提高研究的统计学效力,为下一步探索最佳的甲型H1N1流感疫苗免疫策略的循证决策提供科学数据[1,2].     

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。     

Reduced immune response to influenza A (H1N1) 2009 monovalent vaccine in HIV-infected Japanese subjects

We evaluated the immunogenicity and safety of the influenza A (H1N1) 2009 monovalent vaccine in HIV-infected Japanese subjects. A total of 182 HIV-infected and 42 HIV-uninfected subjects were enrolled, and antibody (ab) titers were measured by hemagglutination-inhibition assay at baseline and 32.3 ± 10.4 and 29.7 ± 3.3 days after vaccination, respectively. In the HIV-infected cohort, ab titers ≥1:40 at baseline and post-vaccination were 12.6% and 49.5%, respectively. The seroconversion rate, defined as either an ab titer ≤1:10 before and ≥1:40 after or ≥1:10 before and ≥4-fold increase in ab titer, was only 38.5% in the HIV-infected cohort, whereas the rate was 85.7% in the HIV-uninfected cohort. Multivariate logistic regression analysis showed that the CD4 cell count was the only significant predictor of a positive vaccine response. There were no serious adverse events in any of the subjects receiving the vaccine. Additional study is warranted to identify a more effective method of vaccinating HIV-infected Japanese subjects.     

孕产妇甲型H1N1流感重症患者临床特征与治疗分析

目的分析孕妇甲型H1N1流感重症患者临床特点、治疗策略,为治疗甲型H1N1流感重症提供理论依据。方法对3例甲型H1N1流感孕产妇重症患者的临床特征、实验室表现、影像学变化和治疗手段进行分析。结果 2例患者进行了剖宫产,1例做了引产,其中1例患者出现脑疝死亡。结论甲型H1N1流感孕产妇疾病发展迅速,并发症多,常合并多脏器衰竭,发病机制复杂,治疗上晚期孕妇及早终止妊娠,积极抗病毒和生命支持治疗至关重要。     

北京市人群甲型H1N1流感血清流行病学调查

目的 了解和掌握北京市人群对甲型H1N1流感的免疫水平.方法 在2009年11月27日至12月23日从医院患者(排除感染科和呼吸科)、血液中心志愿者和体检中心健康体检者中随机选取调查对象进行问卷调查,并采集血清标本进行甲型H1N1流感病毒血凝抑制(HI)抗体检测.结果 共选取调查对象856名,其中127名(14.8%)调查对象体内甲型H1N1流感病毒HI抗体为阳性.0～5岁、6～17岁、18～55岁、≥56岁年龄组HI抗体阳性率分别为14.5%、19.4%、17.4℅和8.0%(P=0.009).不同性别HI抗体阳性率差异无统计学意义(P=0.693).人群血清HI抗体年龄加权阳性率为15.8%.多因素logistic回归分析显示,年龄、出现过急性呼吸道症状以及接种甲型H1N1流感疫苗与HI抗体阳性呈显著性相关.结论 北京市已经有超过15%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.