中国甲型病毒性肝炎疫苗上市后的安全性评价

发布时间：2018-04-17 20:12

本文选题：甲型肝炎减毒活疫苗 + 甲型肝炎灭活疫苗　；参考：《中国疾病预防控制中心》2010年硕士论文

【摘要】： 背景：甲型肝炎(甲肝)减毒活疫苗(Hepatitis A Vaccine, Live,HepA-L)和HepA-I (Hepatitis A Vaccine,Inactivated,HepA-I)上市后疑似预防接种异常反应(Adverse Events Following Immunization, AEFI)监测是评价HepA安全性的重要方法。我国从2005年开展AEFI监测,本文对2007～2008年北京、河北、上海、广东、广西5个省(自治区、直辖市,下同)接种HepA-L和HepA-I后发生的AEFI和严重不良反应(Serious Adverse Reaction)的发生率及特征进行分析,评价两种类型甲肝疫苗上市后的安全性。目的：分析我国5个省接种HepA-L和HepA-I后发生的AEFI和严重不良反应的发生率及特征,评价两种HepA的安全性。方法：通过中国免疫规划监测信息管理系统和儿童预防接种信息管理系统(AEFI监测系统)报告收集2007年1月1日～2008年12月31日接种的HepA-L和HepA-I后发生的AEFI和严重不良反应个案信息,采用描述性方法对严重不良反应的发生率及特征进行流行病学统计分析。结果：从AEFI发生情况看,2007年1月1日～2008年12月31日,5省共报告由HepA AEFI220例,总报告发生率为41.34／100万；报告发病率依次为河北、上海、广东、北京和广西,范围在3.39～274.22／100万；其中不良反应200例,报告发生率为37.61／100万,严重不良反应106例,报告发生率为19.93／100万。HepA-L严重不良反应28例,报告发生率为11.84／100万；HepA-I78例,报告发生率26.41／100万。两种HepA106例严重不良反应中,重度发热(腋温≥38.6℃)53例,报告发生率9.97／100万；过敏反应52例,报告发生率9.78／100万(包括过敏性皮疹41例,报告发生率7.71／100万；过敏性休克1例,报告发生率0.19／100万；其它过敏反应10例,报告发生率1.88／100万)；无菌性脓肿1例,报告发生率0.19／100万。无局部红肿直径5cm、硬结直径5cm、过敏性紫癜、血小板减少性紫癜、阿瑟(Arthus)反应、血管性水肿、多发性神经炎、GBS、臂丛神经炎、癫痫、脑病、脑炎和脑膜炎等严重不良反应。在HepA-L28例严重不良反应中,重度发热15例,报告发生率6.34／100万；过敏反应13例,报告发生率5.50／100万(包括过敏性皮疹11例,报告发生率3.00／100万；过敏性休克1例,报告发生率0.42／100万；其它过敏反应1例,报告发生率0.42／100万)。在HepA-I78例严重不良反应中,高热38例,报告发生率12.87／100万；过敏反应39例,报告发生率13.20／100万(包括过敏性皮疹30例,报告发生率10.16／100万；其它过敏反应9例,报告发生率3.05／100万)；无菌性脓肿1例,报告发生率0.34／100万。从性别构成比看,106例严重不良反应中,男性68例,女性38例,男女性别比为1.79：1。HepA-L的严重不良反应28例,男性22例,女性6例,男女性别比为3.37：1；HepA-I的严重不良反应78例,男性46例,女性32例,男女性别比为1.44：1。从年龄构成比看,HepA的严重不良反应年龄分布情况：1岁1例,占1.28%；1岁为34例,占43.59%；2～6岁43例,占55.13%。HepA-L的严重不良反应为为28例,1岁0例；1～2岁为11例,占39.29%；2～6岁17例,占60.71%。HepA-I的严重不良反应为78例,1岁1例,占1.28%；1～2岁为34例,占43.59%；2-6岁43例,占55.13%。从剂次分布上看,HepA-L28例严重不良反应均是1剂次；在HepA-I78例严重不良反应中,第1剂次为53例,占67.95%,第2剂次25例,占32.05%。 106例严重不良反应中,接种后≤1d发生的为27例,占79.24%；2-3d18例,占16.98%。在HepA-L28例严重不良反应中,接种后≤1d发生的为27例,占96.43%；2～3d1例,占3.57%；在HepA-I78例严重不良反应中接种后≤1d发生的为57例,占73.08%；2～3d17例,占21.79%。从严重不良反应的转归看,106例严重不良反应中,治愈74例,占69.81%；好转29例,占27.36%；无死亡和残留后遗症；不详3例,占2.83%。HepA-L的严重不良反应治愈17例,占60.71%；好转10例,占35.71%；后遗症0例；死亡0例；不详1例,占3.57%。HepA-I的严重不良反应治愈57例,占73.08%；好转19例,占24.363%；后遗症0例；死亡0例；不详2例,占2.56%。 106例严重不良反应住院的个案14例,占13.21%,其中住院≤10d的11例,占10.38%；10d为3例,占2.83%。HepA-L住院个案7例,占43.75%,0～2d为1例,占3.57%,3～5天6例,占21.43%,平均住院天数为3.57天。HepA-I住院个案7例,占8.97%,0～2d为0例,3～5天2例,占2.56%,6～10天2例,占2.56%,11～15天1例,占1.28%,16～30天1例,占1.28%,31～60天1例,占1.28%,平均住院天数为13.71天。从企业发生严重不良反应的构成比看,HepA-L厂商A报告例数为3例,占10.71%；B为9例,占32.14%；C为10例,占35.71%；D为2例,占7.14%；E为4例,占14.29%。HepA-I厂商a报告例数为30例,占38.46%,；b为21例,占26.92%；c为14例,占17.95%；d为7例,占1.75%；e为6例,占7.69%。 HepA-L和HepA-I各生产企业均疫苗严重不良反应以发热(腋温≥38.6℃)和过敏性皮疹为主。各企业疫苗批号未发现聚集性反应。结论：我国接种HepA-L和HepA-I后发生的AEFI和严重不良反应报告发生率均较低。严重不良反应以发热(腋温≥38.6℃)和过敏性反应居多,男性报告发病率高于女性,2-6岁组报告发病率高,多发生在1d内,多在3d内治愈或好转。未报告聚集性反应。 HepA-L严重不良反应报告发生率较HepA-I低,二者均以发热(腋温≥38.6℃)和过敏性反应为主,各年龄组HepA-L严重不良反应报告发生率较HepA-I低,HepA-L严重不良反应住院平均时间较HepA-I短,二者均未报告聚集性反应。
[Abstract]:Background: hepatitis A virus (HAV) attenuated live vaccine (Hepatitis A, Vaccine, Live, HepA-L) and HepA-I (Hepatitis A Vaccine, Inactivated, HepA-I) after the listing of suspected abnormal reaction to vaccination (Adverse Events Following Immunization, AEFI) monitoring is an important method to evaluate the safety of HepA in our country. The development of AEFI monitoring from 2005. In 2007~2008 years in Beijing, Hebei, Shanghai, Guangdong, Guangxi 5 provinces (autonomous regions and municipalities directly under the central government, the same below) occurred HepA-I after inoculated with HepA-L and AEFI and serious adverse reactions (Serious Adverse Reaction) the incidence and characteristics analysis, evaluation of two types of hepatitis A vaccine after the listing of the security.
Objective: to analyze the incidence and characteristics of AEFI and severe adverse reactions in 5 provinces of China after inoculation of HepA-L and HepA-I, and to evaluate the safety of two kinds of HepA.
Methods: the immunization information management system through the China immunization monitoring information management system (AEFI system) and children's information report from January 1, 2007 to December 31, 2008 with HepA-L and HepA-I after AEFI and serious adverse reaction cases, using descriptive methods on the incidence of serious adverse reactions and characteristics were collected and analyzed.
Results: the occurrence of AEFI, from January 1, 2007 to December 31, 2008, 5 provinces were reported by HepA AEFI220 cases, the total incidence was 41.34 / 1 million; the report incidence rate was followed by Hebei, Shanghai, Guangdong, Beijing and Guangxi, in the range of 3.39 ~ 274.22 / 1 million; of which 200 cases of adverse reactions, the incidence of reported as 37.61 106 / 1 million cases of serious adverse reactions, the incidence was 28 cases of serious adverse reactions of the 19.93 / 1 million.HepA-L, the incidence of reported as 11.84 / 1 million; HepA-I78 cases, report the incidence of 26.41 / 1 million.
Two HepA106 cases of serious adverse reactions, severe fever (axillary temperature more than 38.6 DEG C) in 53 cases, the report incidence rate of 9.97 / 1 million; 52 cases of allergic reactions, reported incidence of 9.78 / 1 million (including 41 cases of allergic rash, reported incidence of 7.71 / 1 million; 1 cases of anaphylactic shock report incidence 0.19 / 1 million; 10 cases and other allergic reactions occurred in 1.88 / 1 million) report; 1 cases of aseptic abscess, report the incidence of 0.19 / 1 million. No local swelling and induration diameter 5cm, diameter 5cm, allergic purpura, thrombocytopenic purpura, Arthur (Arthus) reaction, vascular edema, multiple neuritis, GBS, brachial neuritis, seizures, encephalopathy, encephalitis and meningitis and other serious adverse reactions.
In serious adverse reactions in HepA-L28 cases, 15 cases of severe fever, reported incidence of 6.34 / 1 million; 13 cases of allergic reactions, reported incidence of 5.50 / 1 million (including 11 cases of allergic rash, reported incidence of 3 / 1 million; 1 cases of anaphylactic shock reported incidence of 0.42 / 1 million; in 1 cases, other allergy reported incidence of 0.42 / 1 million).
In serious adverse reactions in HepA-I78 cases, 38 cases of high fever, the incidence of 12.87 / 1 million; 39 cases of allergic reactions, reported incidence of 13.20 / 1 million (including 30 cases of allergic rash, reported incidence of 10.16 / 1 million; 9 cases of allergic reactions, other reporting rate 3.05 / 1 million); 1 cases of aseptic abscess the report, the incidence of 0.34 / 1 million.
From the gender perspective, 106 cases of serious adverse reactions, 68 cases were male, 38 were female, male and female sex ratio of serious adverse reactions of 1.79:1.HepA-L in 28 cases, 22 cases were male, 6 female, male to female ratio was 3.37:1; 78 cases of serious adverse reactions of HepA-I, 46 cases were male, 32 cases of female, male and female the sex ratio was 1.44:1.
From the age structure, serious adverse reactions of the age distribution of HepA: 1 years old in 1 cases, accounting for 1.28%; 1 for 34 cases, accounting for 43.59%; 2~6 years old 43 cases of serious adverse reactions of 55.13%.HepA-L for 28 cases, 1 cases at the age of 0; 1~2 of 11 cases, accounting for 39.29%; 2~6 years old in 17 cases, accounting for serious adverse reactions of 60.71%.HepA-I for 78 cases, 1 of 1 cases, accounting for 1.28%; 1~2 for 34 cases, accounting for 43.59%; 2-6 in 43 cases, accounting for 55.13%. from the dose distribution, serious adverse reactions of HepA-L28 cases are 1 doses; serious adverse reactions in HepA-I78 patients. First doses for 53 cases, accounting for 67.95%, second times in 25 cases, accounting for 32.05%.
106 cases of serious adverse reactions occurred in less than 1D after inoculation for 27 cases, accounting for 79.24%; 2-3d18 cases, accounted for 16.98%. of serious adverse reactions occurred in HepA-L28 cases, less than 1D after inoculation for 27 cases, accounting for 96.43%; 2 ~ 3D1 cases, accounting for 3.57%; there is less than or equal to 1D were inoculated in HepA-I78 cases of serious adverse reactions in the 57 cases, accounting for 73.08%; 2 ~ 3d17 cases, accounting for 21.79%.
From the outcome of severe adverse reactions, 106 cases of serious adverse reactions, 74 cases were cured, accounting for 69.81%; 29 cases were improved, 27.36%; no death and residual sequelae; 3 cases were unknown, serious adverse reactions of 2.83%.HepA-L accounted for 60.71%; 17 cases were cured, 10 cases improved, accounting for 35.71%; 0 cases of sequelae; 0 cases died; 1 cases were unknown, serious adverse reactions of 3.57%.HepA-I accounted for 73.08%; 57 cases were cured, 19 cases improved, accounting for 24.363%; 0 cases of sequelae; 0 cases died; 2 cases were unknown, accounting for 2.56%.
106 cases of serious adverse reactions in 14 cases, accounting for 13.21%, of which 11 cases of hospitalization, less than 10d accounted for 10.38%; 3 cases with 10d, accounting for 2.83%.HepA-L hospitalized cases, 7 cases, accounting for 43.75%, 0 ~ 2D for 1 cases, accounting for 3.57%, 3~5 days in 6 cases, accounting for 21.43%, the average hospital stay was 3.57 days.HepA-I in 7 cases, accounting for 8.97%, 0 to 2D for 3~5 days in 0 cases, 2 cases, accounting for 2.56%, 6~10 days in 2 cases, accounting for 2.56%, 11~15 days in 1 cases, accounting for 1.28%, 16~30 days in 1 cases, accounting for 1.28%, 31~60 days in 1 cases, accounting for 1.28%, the average hospital stay was 13.71 days.
The occurrence of serious adverse reactions from the constituent ratio, HepA-L manufacturer A report for 3 cases, accounting for 10.71%; 9 cases with B, accounting for 32.14%; 10 cases with C, accounting for 35.71%; 2 cases with D, accounting for 7.14%; 4 cases with E, accounting for 14.29%.HepA-I manufacturers a report for 30 cases. 38.46%, B; 21 cases, accounting for 26.92%; 14 cases with C, accounting for 17.95%; 7 cases with D, accounting for 1.75%; 6 cases with E, accounting for 7.69%.
HepA-L and HepA-I each production enterprise serious adverse reactions to the vaccine fever (axillary temperature more than 38.6 DEG C) and allergic rash.
No aggregated response was found in the batch number of every enterprise vaccine.
Conclusion: our inoculation of HepA-L and HepA-I after AEFI and reports of severe adverse reactions incidence rate was low. Serious adverse reactions with fever (axillary temperature more than 38.6 DEG C) and the majority of allergic reactions, the reported incidence of male was higher than female, 2-6 years old group reported high incidence occurred in the 1D, how to cure or better in 3D. No aggregation reaction was reported.
HepA-L reports of severe adverse reactions incidence was lower than that of HepA-I, two of them were fever (axillary temperature more than 38.6 DEG C) and allergic reactions, each age group HepA-L reports of severe adverse reactions compared with the incidence of HepA-I is low, serious adverse reactions HepA-L average hospitalization time is short of HepA-I, the two did not report aggregation reaction.

【学位授予单位】：中国疾病预防控制中心
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R186

【参考文献】