Haber Penina, Sejvar James, Mikaeloff Yann, DeStefano Frank
Immunization Safety Office, Office of the Chief Science Officer, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
Drug Saf. 2009;32(4):309-23. doi: 10.2165/00002018-200932040-00005.
Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis in developed countries and is characterized by various degrees of weakness, sensory abnormalities and autonomic dysfunction. Although the underlying aetiology and pathophysiology of GBS are not completely understood, it is broadly believed that immune stimulation plays a role in its pathogenesis. Thus, since vaccines have an effect on the immune system it is biologically plausible that immunizations may be associated with subsequent GBS. The objective of this article is to review the current body of evidence that either supports or does not support a causal, rather than just temporal, association between various vaccines and GBS, and to provide an evidence-based review of this issue. The scope of the article includes published reports that, regardless of method of case ascertainment, appeared in peer-reviewed literature between 1950 and 2008. Our review indicates that, with rare exceptions, associations between vaccines and GBS have been only temporal. There is little evidence to support a causal association with most vaccines. The evidence for a causal association is strongest for the swine influenza vaccine that was used in 1976-77. Studies of influenza vaccines used in subsequent years, however, have found small or no increased risk of GBS. Older formulations of rabies vaccine cultured in mammalian brain tissues have been found to have an increased risk of GBS, but newer formulations of rabies vaccine, derived from chick embryo cells, do not appear to be associated with GBS at a greater than expected rate. In an earlier review, the Institute of Medicine concluded that the evidence favoured a causal association between oral polio vaccine and tetanus toxoid-containing vaccines and GBS. However, recent evidence from large epidemiological studies and mass immunization campaigns in different countries found no correlation between oral polio vaccine or tetanus toxoid-containing vaccines and GBS. Spontaneous reports to the US Vaccine Adverse Events Reporting System shortly after the introduction of quadrivalent conjugated meningococcal vaccine (MCV4) raised concerns of a possible association with GBS. Comparisons with expected rates of GBS, however, were inconclusive for an increased risk, and lack of controlled epidemiological studies makes it difficult to draw conclusions about a causal association. For other vaccines, available data are based on isolated case reports or very small clusters temporally related to immunizations, and no conclusion about causality can be drawn. There are certain circumstances in which immunizing individuals, particularly those with a prior history of GBS, may require caution. However, the benefit of vaccines in preventing disease and decreasing morbidity and mortality, particularly for influenza, needs to be weighed against the potential risk of GBS.
格林-巴利综合征(GBS)是发达国家急性弛缓性麻痹的主要病因,其特征为不同程度的肌无力、感觉异常和自主神经功能障碍。尽管GBS的潜在病因和病理生理学尚未完全明确,但人们普遍认为免疫刺激在其发病机制中起作用。因此,由于疫苗会影响免疫系统,从生物学角度来看,免疫接种可能与随后发生的GBS有关。本文的目的是综述当前支持或不支持各种疫苗与GBS之间存在因果关系(而非仅仅是时间上的关联)的证据,并对该问题进行基于证据的综述。本文的范围包括1950年至2008年间发表在同行评审文献中的报告,无论病例确定方法如何。我们的综述表明,除极少数例外情况外,疫苗与GBS之间的关联仅为时间上的。几乎没有证据支持与大多数疫苗存在因果关系。1976 - 1977年使用的猪流感疫苗存在因果关系的证据最为确凿。然而,对随后几年使用的流感疫苗的研究发现,GBS风险略有增加或没有增加。已发现用哺乳动物脑组织培养的旧版狂犬病疫苗GBS风险增加,但源自鸡胚细胞的新版狂犬病疫苗似乎与GBS的关联率并未高于预期。在早期的一项综述中,美国医学研究所得出结论,证据支持口服脊髓灰质炎疫苗和含破伤风类毒素疫苗与GBS之间存在因果关系。然而,近期来自不同国家的大型流行病学研究和大规模免疫接种活动的证据表明,口服脊髓灰质炎疫苗或含破伤风类毒素疫苗与GBS之间没有相关性。四价结合脑膜炎球菌疫苗(MCV4)引入后不久向美国疫苗不良事件报告系统的自发报告引发了对其与GBS可能存在关联的担忧。然而,与GBS预期发生率的比较对于风险增加的结论并不明确,并且缺乏对照流行病学研究使得难以就因果关系得出结论。对于其他疫苗,现有数据基于与免疫接种在时间上相关的个别病例报告或非常小的病例组,无法得出关于因果关系的结论。在某些情况下,对个体进行免疫接种,特别是那些有GBS既往史的个体,可能需要谨慎。然而,疫苗在预防疾病以及降低发病率和死亡率方面的益处,尤其是对流感而言,需要与GBS的潜在风险进行权衡。