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疫苗的制备
获准使用的脑膜炎球菌疫苗是根据标准要求用净化的细菌荚膜多糖制成的(who,1976a)。现有产品包括单价的a或c组,二价的a+c或三价的a+c+y+w135多糖疫苗。冻干制剂在注射前进行还原,稀释剂可包括很小剂量的硫柳汞。一剂疫苗中每种抗原的含量通常为50微克,疫苗用于皮下注射。免疫产生一种血清群特定抗体反应,可用于控制范围广泛的流行病和局部疾病暴发以及预防高危个体中出现散发性的脑膜炎球菌病例。联合王国最近引进了针对丙型脑膜炎球菌的一种共轭疫苗,并在大规模免疫接种活动中予以使用。
轻度局部反应
评估疫苗不良反应发生率的“黄金标准”是双盲随机取样实验,对照组注射含有一种无活性物质的安慰剂。出于伦理方面显而易见的原因,这种研究设计从未用于脑膜炎球菌疫苗试用,对照组注射另一种疫苗或者不进行注射。在使用一剂或两剂注射计划的所有对照实验中,对多糖疫苗的耐受情况良好,未发现任何严重反应(who,1976b)。局部反应较常见(在一次研究中多达接种者的71%)但较轻微,主要包括持续1-2天的局部红斑(makela等,1975;makela等,1977;peltola等,1978;griffiss等,1981;hankins等,1982;ambrosch等,1983;peltola等,1985;lepow等,1986;lieberman等,1996;king等,1996)。
全身性反应
反热是多糖疫苗最一贯性的全身性反应。在对照实验中,报道的体温达到或超过38.5℃的短暂发热反应发生率在0.6%与3.6%之间(makela等,1977;hankins等,1982;king等,1996;lieberman等,1996)。已发现全身性反应的发生率和严重程度与整批疫苗的残留细菌内毒素含量之间存在联系(peltola等,1978)。但是,目前的多糖疫苗经过高度净化,全身性反应较少见。在1993年魁北克的一次主要使用一种二价a+c疫苗的大规模免疫接种活动期间,报告的发热发生率为1.9%,但真实数字可能更低些(saintonge,1995)。在同一次免疫接种活动期间,所有过敏反应的发生率为每10万剂9.2例,约120万疫苗接种者中仅发生1例非致命的过敏反应(yergeau等,1996)。为新西兰,在130 000名儿童接种疫苗后有92人报告了短暂的外围运动和感觉神经症状(hood等,1989)。但是,报告是在通过媒体宣布正在征求对脑膜炎球菌疫苗反应的报告之后由家长提供的,只有少数几例经过医学评估。因此,难以确立因果关系。
已发表的关于反复接种疫苗的数据很少。在对儿童进行的两次小型研究中,第二和第三剂之后并未出现比最初的免疫接种之后更高的局部和全身性反应发生率(gold等,1979;macdonald等,1998)。
其它影响
多糖疫苗在幼儿中产生相对较差的免疫反应。在加拿大最近的一次研究中,有证据表明年龄为15-23个月时进行免疫接种的儿童在12个月以后接种第二剂,可对c组多糖产生血清反应不足(macdonald等,1998)。在成人中也观察到对c组多糖的免疫不应性(granoff等,1998)。但是,这种现象的临床意义尚不清楚。迄今,在经过免疫接种的个体中,甚至在两岁之前接受第一剂的个体中,未观察到c组脑膜炎球菌疾病风险的任何增长(taunay等,1978;de wals等,1996)。灭活疫苗被认为对胎儿是安全的。在母亲于妊娠期间接种过脑膜炎球菌疾病疫苗的51名新生儿中,未记录到任何不良影响(mccormick等,1980)。
参考文献
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