Geier Mark R, Geier David A, Zahalsky Arthur C
The Genetic Centers of America, 14 Redgate Court, Silver Spring, MD 20905, USA.
Clin Immunol. 2003 May;107(2):116-21. doi: 10.1016/s1521-6616(03)00046-9.
Acute and severe Guillain Barre Syndrome (GBS) cases reported following influenza vaccine to the Vaccine Adverse Events Reporting System (VAERS) database from 1991 through 1999 were examined. Endotoxin concentrations were measured using the Limulus amebocyte lysate assay in influenza vaccines. There were a total of 382 cases of GBS reported to the VAERS database following influenza vaccination (male/female ratio, 1.2). The median onset of GBS following influenza vaccine was 12 days (interquartile range, 7 days to 21 days). There was an increased risk of acute GBS (relative risk, 4.3; 95% confidence interval, 3.0 to 6.4) and severe GBS (relative risk, 8.5; 95% confidence interval, 3.7 to 18.9) in comparison to an adult tetanus-diphtheria (Td) vaccine control group. There were maximums in the incidence of GBS following influenza vaccine that occurred approximately every third year (1993, 1996, and 1998) and statistically significant variation in the incidence of GBS among different influenza manufacturers. Influenza vaccines contained from a 125- to a 1250-fold increase in endotoxin concentrations in comparison to an adult Td vaccine control and endotoxin concentrations varied up to 10-fold among different lots and manufacturers of influenza vaccine. The biologic mechanism for GBS following influenza vaccine may involve the synergistic effects of endotoxin and vaccine-induced autoimmunity. There were minimal potential reporting biases in the data reported to the VAERS database in this study. Patients should make an informed consent decision on whether to take this optional vaccine based upon its safety and efficacy and physicians should vigilantly report GBS following influenza vaccination to the VAERS in the United States so that continued evaluation of the safety of influenza vaccine may be undertaken.
对1991年至1999年向疫苗不良事件报告系统（VAERS）数据库报告的流感疫苗接种后急性和严重格林-巴利综合征（GBS）病例进行了检查。使用鲎试剂法测定流感疫苗中的内毒素浓度。共有382例GBS病例在流感疫苗接种后报告至VAERS数据库（男女比例为1.2）。流感疫苗接种后GBS的中位发病时间为12天（四分位间距为7天至21天）。与成人破伤风-白喉（Td）疫苗对照组相比，急性GBS（相对风险，4.3；95%置信区间，3.0至6.4）和严重GBS（相对风险，8.5；95%置信区间，3.7至18.9）的风险增加。流感疫苗接种后GBS发病率大约每三年出现一次高峰（1993年、1996年和1998年），并且不同流感疫苗生产商之间GBS发病率存在统计学显著差异。与成人Td疫苗对照组相比，流感疫苗中的内毒素浓度增加了125至1250倍，不同批次和生产商的流感疫苗内毒素浓度差异高达10倍。流感疫苗接种后GBS的生物学机制可能涉及内毒素和疫苗诱导的自身免疫的协同作用。本研究中向VAERS数据库报告的数据存在最小的潜在报告偏倚。患者应基于流感疫苗的安全性和有效性就是否接种这种非必需疫苗做出知情同意决定，并且医生应在美国向VAERS警惕地报告流感疫苗接种后的GBS病例，以便能够持续评估流感疫苗的安全性。
