季节性流感疫苗免疫者更易感H1N1

Did seasonal flu vaccination increase the risk of infection with pandemic H1N1 flu?
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In September 2009, news stories reported that researchers in Canada had found an increased risk of pandemic H1N1 (pH1N1) influenza in people who had previously been vaccinated against seasonal influenza. Their research, consisting of four different studies, has now undergone further scientific peer review and is published in the open access journal PLoS Medicine.
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6 C8 f+ N% F2 D6 K  XDid previous vaccination against seasonal flu increase the risk of getting pH1N1 flu? Based on these studies -- conducted by a large network of investigators across Canada led by Principal Investigator Danuta Skowronski of the British Columbia Centre for Disease Control in Vancouver, in collaboration with provincial leads Gaston De Serres in Quebec, Natasha Crowcroft in Ontario and Jim Dickinson in Alberta -- the answer remains: "possibly."
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4 y1 P6 d# U& Z3 nIn a school outbreak of pH1N1 in spring 2009, people with cough and fever were found to have received prior seasonal flu vaccination more often than those without. Several public health agencies in Canada therefore undertook four additional studies during the summer of 2009 to investigate further. Taken together, the four studies included approximately 2,700 people with and without pH1N1.
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4 G* S3 _; o$ s9 gThe first of the studies used an ongoing sentinel monitoring system to assess the frequency of prior vaccination with the 2008-09 seasonal vaccine in people with pH1N1 influenza (cases) compared to people without evidence of infection with an influenza virus (controls). This study confirmed that the seasonal vaccine provided protection against seasonal influenza, but found it to be associated with an increased risk of approximately 68% for pH1N1 disease.
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The further 3 studies (which included additional case-control investigations in Ontario and Quebec, as well as a transmission study in 47 Quebec households where pH1N1 influenza had occurred) similarly found between 1.4-2.5 times increased likelihood of pH1N1 illness in people who had received the seasonal vaccine compared to those who had not. Prior seasonal vaccination was not associated with an increase in hospitalization among those who developed pH1N1 illness.
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; ^: d% v, H% X6 x& s, mThese studies do not show whether there was a true cause-and-effect relationship between seasonal flu vaccination and subsequent pH1N1 illness (as might occur if, for example, the seasonal vaccine modified the immune response to pH1N1), or whether the observed association was not a result of vaccination, but was instead due to differences in some unidentified factor among the groups being studied.

If the findings from these studies are real they raise important questions about the biological interactions between pre-existing and novel pandemic influenza strains. The researchers note, however, that the World Health Organization has recommended that pH1N1 be included in subsequent seasonal vaccine formulations. This will provide direct protection against pH1N1 and thereby obviate any risk that might have been due to the seasonal vaccine in 2009, which did not include pH1N1.
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In an accompanying commentary in PLoS Medicine, Lone Simonsen and Cécile Viboud, who were not involved in the studies, write: "Given the uncertainty associated with observational studies, we believe it would be premature to conclude that increased the risk of 2009 pandemic illness, especially in light of six other contemporaneous observational studies in civilian populations that have produced highly conflicting results." They conclude that "this perplexing experience should teach us how to best react to disparate and conflicting studies and prepare us for the next public health crisis, so that we can better manage future alerts for unexpected risk factors."

Funding: This project was funded by the Canadian Institutes of Health Research, the British Columbia Ministry of Health and the British Columbia Centre for Disease Control, Alberta Health and Wellness, the Ontario Agency for Health Protection and Promotion, the Ontario Ministry of Health and Long Term Care, the Ministère de la santé et des services sociaux du Québec, the Institut national de santé publique du Québec and the Fonds de la recherche en santé du Québec (FRSQ). Although agencies of the investigators provided infrastructure in support of the reported studies, the funders did not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
& j+ h: u9 B. i/ r- qhttp://www.sciencedaily.com/releases/2010/04/100406172635.htm
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接种季节性流感疫苗会增加被H1N1感染的风险吗？
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7 ~2 V3 {" Q" A1 V2009年9月，加拿大的研究人员报道称，他们发现曾接种过季节性流感疫苗的人被H1N1病毒感染的几率会更高。此项研究分四个不同方面，其结果已经通过同行评审并发表在免费期刊PLoS Medicine（美国公共科学图书馆杂志—医学分册）上。
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接种季节性流感疫苗真的会增加被H1N1感染的风险吗？结论是“可能”。此研究的主持人Danuta Skowronski（加拿大华英属哥伦比亚疾病控制中心温哥分中心）与Gaston De Serres（魁北克分），Natasha Crowcroft（安大略）以及Jim Dickinson（阿尔伯塔）展开全国性合作研究，得出这一结论。
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. Q- g: `1 {4 z  w9 A% F8 g/ S) ?2009年春季，一所学校曾爆发H1N1，那些曾经常接种季节性流感疫苗的病人会伴有咳嗽和发烧，而那些接种季节性疫苗相对很少的人却没有这两种症状。因此，2009年夏天，加拿大的几家公共健康机构就四方面进一步展开研究。这一研究的对象包括2700人，其中有感染H1N1的，还有没有被感染的。

) y, v6 W0 R  s. u, ^+ ?研究的一方面是利用标记监控系统评价那些感染H1N1的人（患者）在2008—2009期间接种季节性疫苗的次数，同时记录没有 H1N1感染症状的人（对照组）的接种次数。这一研究的结果表明接种季节性流感疫苗的确可以有效防止季节性流感病毒感染，但是却增加了H1N1感染的几率（最大可达68%）。
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另外三方面研究（包括在安大略和魁北克开展的“发病—无病”比较研究以及在魁北克开展的47个感染H1N1的家庭的转染情况研究）也证实接种季节性流感疫苗会将H1N1感染几率增加1.4到2.5倍。接种季节性疫苗与H1N1患者住院率的升高无关。

这些研究并没有发现接种季节性疫苗和H1N1感染存在确切的因果关系（如果有，可能的原意之一是接种季节性流感疫苗改变了机体对H1N1的免疫反应），而且研究并没有发现除了接种季节性疫苗以外的潜在因素。

* M% q7 b% ]. @8 e1 ?& b, @7 w. g如果这些研究结论是正确的，那么就为我们提出了一个重要问题——现存的流感毒株与新的大流行性流感毒株的生物学关系。但是，研究人员说世卫组织已经建议将 H1N1列入下一步的季节性流感免疫范畴。这将直接对H1N1产生免疫保护，免除了2009年接种季节性疫苗（不包括H1N1）所造成的危险。
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! x; |0 {* Y1 o% n在PLoS Medicine杂志的一篇评论文章中，Lone Simonsen和Cécile Viboud（并没有参与上述研究）写道，“基于科学研究结果的不确定性，尤其是其他6项在平民中开展的同期研究所得到的结果非常不一致，所以现在就对 2009大流行感冒的危险因素下结论还为时尚早。这一次复杂告诉我们应该知道如何看待各种科学研究所得到的结果（这些结果甚至是相互矛盾的），做好应对下一次公共健康危机的准备，这样我们就可以更好地处理可能再次发生的意外危险预警。”
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0 ]8 z- W! B3 E' R' ~; K9 E资金支持：本项目由加拿大健康研究所，英属哥伦比亚健康部，英属哥伦比亚疾病控制中心，阿尔伯塔健康中心，安大略健康保护和促进机构，安大略健康和长期医护部，魁北克健康和社会服务部，魁北克国家公共健康研究所，魁北克健康研究基金（FRSQ）共同资助。虽然这些资助机构为研究人员提供了研究所需的基础设施，但是并没有干预研究的实验设计，数据采集分析以及论文撰稿和发表工作。
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