《疫苗安全的信息》doc版.doc

精品文档 免费阅读 免费分享 如需请下载！ 请下载！ 关于疫苗安全的关于疫苗安全的 补充信息补充信息 第 2 部分：免疫接种后的 不良事件基础发生率 疫苗和生物制品司疫苗和生物制品司 世界卫生组织 日内瓦 2000年 ii 疫苗和生物制品司疫苗和生物制品司 感谢提供非特定经济支持的捐助者，感谢提供非特定经济支持的捐助者， 他们的支持使之有可能出版这份文件。他们的支持使之有可能出版这份文件。 有些数据来自原先由世界卫生组织 西太平洋区域办事处扩大免疫规划编写的材料 本文件由疫苗和生物制品司 扩大免疫规划处编写 C.J. Clements 博士编辑博士编辑 订购编号：WHO/V family history of convulsions and use of antipyretics. MMWR: Morbidity and Mortality Weekly Report, 36:2812. CDC (1996) Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP). Update: vaccine side effects, adverse reactions, contraindications and precautions. MMWR: Morbidity and Mortality Weekly Report, 45(RR-12):2231. CDC (1997). Centers for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP). Pertussis Vaccination: Use of acellular pertussis vaccines among Infants and young children. MMWR: Morbidity and Mortality Weekly Report, 46(RR-7):116. Cherry JD (1996). Historical review of pertussis and the classical vaccine. Journal of Infectious Diseases, 174,supt 3:S259S263. Cody CL, Baraff LJ, Cherry JD, et al. (1981). Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children. Pediatrics, 68:650 60. Decker MM, Edwards KM, Steinhoff MC, et al. (1995). Comparison of 13 acellular pertussis vaccines: adverse reactions. Pediatrics, 96:55766. Decker MM, Edwards KM (1996). The multicenter acellular pertussis trial: An overview. Journal of Infectious Diseases, 174, supt 3:S270S275. Edsall G, Altman JS, Gaspar AJ (1954). Combined tetanus-diphtheria immunization of adults: Use of small doses of diphtheria toxoid. American Journal of Public Health, 44:153745. Edwards KM, Decker MD, Mortimer Jr EA (1999). Pertussis vaccine. In Plotkin S, Orenstein W, eds. Vaccines, 3rd ed., WB Saunders Company, 1999:293-344. WER (1982). Expanded Programme on Immunization. Reactions to tetanus toxoid. Weekly Epidemiological Record, 57:1934. Farrington P, Pugh S, Colville A et al. (1995). A new method for active surveillance of adverse events from DTP and MMR vaccines. Lancet, 345: 5679. 24免疫接种后的不良事件基础发生率 Feldman S, Perry S, Andrew M, et al. (1992). Comparison of acellular (B type) and whole-cell pertussis component diphtheria-tetanus-pertussis vaccines as the first booster immunization in 1524 month-old children. Journal of Pediatrics, 121:85761. Gupta RK, Relyveld EH (1991). Adverse reactions after injection of adsorbed diphtheria-pertussis-tetanus (DPT) vaccine are not due only to pertussis organisms or pertussis components in the vaccine. Vaccine, 9:abstract. Gustafsson L, Hallander HO, Olin P, et al. (1996). A controlled trial of a two- component acellular, a five-component acellular, and a whole-cell pertussis vaccine. New England Journal of Medicine, 334:34955. Halperin SA, Eastwood BJ, Barreto L, et al. (1996). Adverse reactions and antibody response to four doses of acellular or whole cell pertussis vaccine combined with diphtheria and tetanus toxoids in the first 19 months of life. Vaccine, 14:76772. Ipp MM et al. (1987). Acetaminophen prophylaxis of adverse reactions following vaccination of infants with diphtheria-pertussis-tetanus toxoids-polio vaccine. Pediatric Infectious Disease Journal, 6:7215. Ipp MM, Gold R, Goldbach M, et al. (1989). Adverse reactions to diphtheria, tetanus, pertussis-polio vaccination at 18 months of age: effect of injection site and needle length. Pediatrics, 83:67982. Livengood JR, Mullen JR, White JW, et al. (1989). Family history of convulsions and use of pertussis vaccine. Journal of Pediatrics, 115:52731. Long S, Deforest A, Smith DG, et al. (1990). Longitudinal study of adverse reactions following diphtheria-tetanus-pertussis vaccine in infancy. Pediatrics, 85:294302. Mark A, Carlsson RM, Granstrom M (1999). Subcutaneous versus intramuscular injection for booster DT vaccination of adolescents. Vaccine, 17:206772. Mills E, Gold R, Thipphawong J, et al (1998). Safety and immunogenicity of a combined five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus b conjugate vaccine administered to infants at two, four and six months of age. Vaccine, 16:57685. Mortimer Jr EA, Kharton M (1999). Diphtheria toxoid. in Plotkin S, Orenstein W. Vaccines, 3rd ed. Philadelphia, PA, WB Saunders Company, 1999:140157. Myers MG, Beckman CW, Vosdingh RA et al. (1982). Primary immunization with tetanus and diphtheria toxoids. Reactions rate and immunogenicity in older children and adults. JAMA: The Journal of the American Medical Association, 248:247880. WHO/V 104:3436. Barry DW, Mayner RE, Hochstein HD, et al (1976). Comparative trial of influenza vaccines. II. Adverse reactions in children and adults. American Journal of Epidemiology, 104:4759. Bierman CW, Shapiro GG, Pierson WE, et al. (1997). Safety of influenza vaccine in allergic children. Journal of Infectious Diseases, 136:S652S655. WHO/V 181(1):215-21. WHO/V Kemp 等, 1990; James 等, 1995）。因此，蛋过敏史不再被认为是含 麻疹疫苗免疫的一个禁忌症。 脑病脑病/ /脑炎脑炎 麻疹野病毒感染在约千分之一受感染者中引起感染后脑脊髓炎。其中至少 50%的 受感染者留下永久性中枢神经系统损伤。由于微静脉周脱髓鞘损伤，该综合征被认 为是由免疫间介作用产生的。虽然许多人关注麻疹减毒疫苗产生这一综合征的能 WHO/V Duclos, 1998）。风险为每百万份疫苗不到一例， 或比麻疹风险低一千倍左右。 亚急性硬化性全脑炎亚急性硬化性全脑炎 正如在普遍进行麻疹疫苗接种之后亚急性硬化性全脑炎病例接近消灭所证明的， 麻疹疫苗接种减少亚急性硬化性全脑炎的发生（Dyken 等, 1989）。使用一种含有麻 疹活病毒的疫苗即使在以前有麻疹疾病或麻疹疫苗接种史的个体中不会增加患亚 急性硬化性全脑炎的风险（Howson 等, 1991; Duclos 和 Ward, 1998）。 急性热病性多神经炎急性热病性多神经炎 已有在接受麻疹、腮腺炎和风疹及其成份疫苗接种后患急性热病性多神经炎的报 告。但是，美国医学研究院审查了现有研究并认为没有足够的证据接受或拒绝一种 因果关系（Stratton 等, 1994）。最近发表的研究也未能显示因果关联（Hughes 等, 1996, Silveira 等, 1997）。 癫痫发作癫痫发作 在极少情况下，使用一种含麻疹的疫苗可引起热性癫痫发作。通过将联合王国 5 个 地区疫苗接种记录与计算机化医院住院记录相联系，Farrington 等（1995）发现，在 麻疹、腮腺炎和风疹疫苗接种后 6-11 天因发热性惊厥而住院的病人中，有 67%是 由疫苗中的麻疹成份引起的（风险为每 3000 份疫苗一例）。尚未确定麻疹、腮腺炎 和风疹疫苗与残留癫痫发作疾患之间的关联（Stratton 等, 1994）。有个人或家庭癫 痫发作史的儿童面临突发性癫痫的更大风险，但是，在疫苗接种后热性癫痫发作并 不增加这些儿童患癫痫或其它神经疾患的可能性。有惊厥史的儿童可能在麻疹、腮 腺炎和风疹疫苗接种后更多面临发热性惊厥的风险，但此种风险似乎极小 （CDC，1989）。 免疫接种后的不良事件基础发生率 58 血小板减少症血小板减少症 在极少情况下，含有麻疹、腮腺炎和风疹抗原的疫苗可引起血小板减少症。在麻疹、 腮腺炎和风疹疫苗接种后血小板减少症的风险为接种儿童的三万分之一至四万分 之一（Bottiger 等, 1987; Nieminen 等, 1993; Farrington 等, 1995）。这些病例的临床病 程通常是短暂而温和的（Beeler 等, 1996）。对于以前诊断有免疫性血小板减少性紫 癜的人、尤其是在早先一次麻疹、腮腺炎和风疹疫苗接种后患该病的人而言，在麻 疹、腮腺炎和风疹疫苗接种后血小板减少症的风险可能增加（Stratton 等， 1994；Drachtman 等，1994；Vlacha 等，1996）。这些数据支持与麻疹、腮腺炎和风疹 疫苗而不是与麻疹成份的一种因果关系。换言之，不可能将这些反应归因于该疫苗 的任何一种病毒成份。虽然根据天然疾病史，大概更可能与麻疹或风疹成份相联系。 表 5 强调这一事实，即天然麻疹是一种严重疾病，经常发生并发症，而减毒活病毒 疫苗接种则非常温和。 表表 5：在具免疫能力的个体中天然麻疹感染的并发症风险：在具免疫能力的个体中天然麻疹感染的并发症风险 与减毒活病毒疫苗接种已知风险的比较与减毒活病毒疫苗接种已知风险的比较 （在Duclos和Ward之后，1998） 并发症并发症天然疾病后的风险天然疾病后的风险*a)免疫接种后的风险免疫接种后的风险 b) 中耳炎7-9%0 肺炎1-6%0 腹泻6%0 感染后脑脊髓炎0.5-1/10001/1000 000 亚急性硬化性全脑炎1/100 0000 血小板减少症-c)1/30 000d) 死亡0.1-1/1000（在发展中国家 高达 5-15%） 0 * 如在工业化国家所衡量的风险。在发展中国家的风险尚未确定，但普遍较高（Hussey 等， 1996）。 a) 天然麻疹后的风险以案例数的事件计算。 b) 免疫接种后的风险以剂量数的事件计算。 c) 虽然有关于麻疹后发生血小板减少症包括出血的若干报告，但是尚不能对风险进行恰当量化。 d) 这一风险在麻疹、腮腺炎和风疹疫苗接种后有报告，并且不能只归因于麻疹成份。 WHO/V Ekbom 等，1996）。一个研究小组推测，麻疹疫苗可能与 炎性肠病和孤独症的形成有关（Wakefield 等，1998）。在科学界，已就研究中采用的 这些假设所依据的方法局限提出问题（Patriarca 和 Beeler，1995；Farrington 和 Miller，1995；MacDonald, 1995; Miller 和 Renton, 1995; Chen 和 DeStefano, 1998）。 其它研究并不支持这些假设联系（Liu 等，1995；Iizuka 等，1995；Feeney 等， 1997；Haga 等，1996）。没有证据表明麻疹、腮腺炎和风疹疫苗与炎性肠病或孤独症 之间的联系。麻疹疫苗接种与局限性回肠炎和孤独症之间的所谓联系是以薄弱的 科学性为基础的，并已被大量具有坚实科学性的工作所驳斥（Duclos 和 Ward，1998）。 b)腮腺炎疫苗腮腺炎疫苗 轻度不良事件轻度不良事件 在接种含有腮腺炎抗原的疫苗后局部反应是常见的。在接种后 24 小时内，受接种 者可能感觉疼痛和注射部位触痛。这些反应普遍较轻并且是短暂的。在大多数情况 下，它们在 2 至 3 天内自行消失，不需要进一步医疗。使用这些疫苗时，还可能发 生轻度全身性反应。最常见的副作用包括腮腺炎和低烧。腮腺炎通常发生在接种 后 10-14 天（Fescharek 等，1990）。 一般说来，轻度事件的发生率似乎在各株之间差别不大。例如，1.6%接受 Jeryl Lynn 疫苗的儿童和 1-2%接受 Urabe 疫苗的儿童发生腮腺和/或颌下肿胀（Popow- Kraupp 等，1986）。但是，加拿大销售后监测的数据表明 Urabe 株比 Jeryl Lynn 株 的腮腺炎发生率要高得多。 腮腺炎疫苗还与皮疹、瘙痒和紫癜有关，但这些反应并不常见。在腮腺炎疫苗接种 后还可能发生睾丸炎（Kuczyk 等，1994）、关节炎（Nakayama 等，1990；Nussinovitch 等，1995）、感觉神经性聋症（Stewart 和 Prabhu，1993；Nabe-Nielsen 和 Walter，1988）和急性肌炎（Rose 等，1996），这在生物学上似乎是合理的，但是，这 些反应极为罕见。加拿大销售后监测数据显示 Urabe 株比 Jeryl Lynn 株具有更高的 睾丸炎风险，尽管这种风险很小。 免疫接种后的不良事件基础发生率 60 严重不良事件严重不良事件 无菌性脑膜炎无菌性脑膜炎 若干腮腺炎减毒疫苗与无菌性脑膜炎有联系。免疫后潜伏期为 2-3 周，临床病程与 天然疾病类似（McDonald 等，1989）。形成这一并发症的风险因疫苗株和生产厂家 的不同而产生差异： Jeryl Lynn 株。株。该株尚未显示引起无菌性脑膜炎。在美国，一项腮腺炎住院病 例 10 年回顾研究发现在年龄为 12-23 个月的儿童中每 10 万份含 Jeryl Lynn 株 的麻疹、腮腺炎和风疹疫苗只有 1 例无菌性脑膜炎（Black 等，1997）。另一项研 究发现每接种 180 万份有 1 例无菌性脑膜炎（Nalin，1992）。在又一项研究中， 它与每 10 万份 0.1 例病例有关（Fescharek 等，1990）。这是如此罕见的事件，以 致结合疫苗接种发生时，可能是一种巧合。 Leningrad-3 株。株。在腮腺炎疫苗的 Urabe、Leningrad-3 和 L-Z 株与无菌性脑膜 炎之间已确立因果关系（Miller 等，1993；Stratton 等，1994；Black 等，1997; Galazka 等，1999）。在斯洛文尼亚，1979-85 年期间被动监测查明了每 10 万份 含 Leningrad-3 株麻疹和腮腺炎疫苗 20-100 例无菌性脑膜炎（Kraigher, 1990; M.Cizman 等，1989）。 Leningrad-Zagreb(LZ)株。株。1998 年在巴西一次免疫运动期间使用该株之后报 告了无菌性脑膜炎的暴发。在暴发的高峰周期间观察到发病率为每 10 万人口 4.22-1.36 例，发病率比免疫运动前高 70 倍（Dourado，2000）。在斯洛文尼亚记 录的发病率为每 10 万份 20 例（Fescharek 等，1990）。在斯洛文尼亚，报告每 10 万份 2 例无菌性脑膜炎（A. Kraigher，未发表的数据）。在克罗地亚，报告了每 10 万份 90 例（Tesovic 等，1993）。 Rubini 株。株。该株的免疫原性相对较低，并且在 Rubini 株接种后未普遍报告无 菌性脑膜炎是一个问题。但是，在意大利，一项案例对照研究发现，接种 Rubini 株的儿童感染腮腺炎的风险高于使用 Urabe 或 Jeryl Lynn 疫苗 （Benevento，1998）。在葡萄牙，虽然麻疹、腮腺炎和风疹疫苗的覆盖率高，但是 腮腺炎继续大规模流行。在葡萄牙转向使用含 Rubini 株的麻疹、腮腺炎和风疹 疫苗后腮腺炎发病率达到最高峰（Dias 等，1996）。 WHO/V 818-822. Black S, Shinefield H, Ray P, et al. (1997). Risk of hospitalization because of aseptic meningitis after measlesmumpsrubella vaccination in one- to two- year old children: an analysis of the Vaccine Safety Datalink (VSD) Project. Pediatric Infectious Disease Journal, 16: 5003. 免疫接种后的不良事件基础发生率 64 Bottiger M, Christenson B, Romanus V, Taranger J, Strandell A (1987). Swedish experience of two-dose vaccination programme aiming at eliminating measles, mumps, and rubella. British Medical Journal (Clin Res Ed), 295:12647. Buynak EB, Hilleman MR (1966). Live attenuated mumps virus 1. Vaccine development. Proceedings of the Society for Experimental Biology and Medicine, 123:7. CDC (1989). 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