Piedra Pedro A, Yan Lihan, Kotloff Karen, Zangwill Ken, Bernstein David I, King James, Treanor John, Munoz Flor, Wolff Mark, Cho Iksung, Mendelman Paul M, Cordova Julie, Belshe Robert B
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
Pediatrics. 2002 Oct;110(4):662-72. doi: 10.1542/peds.110.4.662.
To provide additional information on the safety of trivalent, cold-adapted influenza vaccine (CAIV-T) in children.
Children 15 to 71 months of age were enrolled in a multicenter, prospective, randomized, double-blind, and placebo-controlled trial to receive by nasal spray CAIV-T or placebo. In year 1 (1996-1997), 1314 were enrolled in the 2-dose cohort and 288 were enrolled in the 1-dose cohort. In year 2 (1997-1998), 1358 of the original participants received 1 dose of vaccine or placebo according to their original treatment group assignment. In year 3 (1998-1999) and year 4, the trial continued as an open-label safety trial of CAIV-T. A total of 642 and 549 children enrolled in years 3 and 4, respectively, received their third and fourth sequential annual doses of CAIV-T. Measured were 1) the occurrence of specific respiratory, gastrointestinal and systemic symptoms, unexpected symptoms (not specified in the diary card), and use of medications within the first 10 days after vaccination; 2) the occurrence of an acute illness and use of medication within 11 to 42 days after vaccination; and 3) the occurrence of serious adverse events within 42 days after vaccination.
The adjusted odd ratios of specific respiratory and gastrointestinal symptoms during the 10 days after vaccination were determined in years 1 and 2. Runny nose or nasal congestion, vomiting, muscle aches, and fever were significantly associated with the first dose of CAIV-T. With the second dose, runny nose was the only symptom that was associated with CAIV-T. In year 2, CAIV-T did not cause excess in any of the specific respiratory and gastrointestinal symptoms. In years 3 and 4, specific respiratory and gastrointestinal symptoms were comparable to that observed in year 2. A CAIV-T-associated symptom was most likely to occur on day 2 with the first dose of vaccine. The occurrence of unexpected symptoms was primarily of the gastrointestinal system. Approximately 6% of CAIV-T and 3.6% of placebo recipients had a gastrointestinal symptom. CAIV-T seemed to be associated with a mild excess in abdominal pain and vomiting only with the first vaccine dose. A statistically significant increase in the use of analgesics/antipyretics was detected only with the first dose in CAIV-T vaccinees compared with placebo recipients (23.5% vs 16.6%). Between days 11 and 42, CAIV-T use was not associated with an excess of illness, otitis media, or use of medication. None of the 6 serious adverse events in CAIV-T recipients in years 1 to 4 was attributed to the vaccine.
CAIV-T was safe in children. Mild respiratory, gastrointestinal, and systemic symptoms of short duration were observed in a minority of children and primarily with the first vaccine dose. Sequential annual doses of CAIV-T were well tolerated.
提供关于三价冷适应流感疫苗（CAIV-T）在儿童中安全性的更多信息。
15至71个月大的儿童参加了一项多中心、前瞻性、随机、双盲、安慰剂对照试验，通过鼻喷雾接种CAIV-T或安慰剂。在第1年（1996 - 1997年），1314名儿童被纳入2剂队列，288名儿童被纳入1剂队列。在第2年（1997 - 1998年），1358名原参与者根据其原治疗组分配接受1剂疫苗或安慰剂。在第3年（1998 - 1999年）和第4年，该试验作为CAIV-T的开放标签安全性试验继续进行。第3年和第4年分别有642名和549名儿童登记，接受了连续第三剂和第四剂年度CAIV-T。测量了：1）接种疫苗后前10天内特定呼吸道、胃肠道和全身症状、意外症状（日记卡中未明确列出）的发生情况以及药物使用情况；2）接种疫苗后11至42天内急性疾病的发生情况和药物使用情况；3）接种疫苗后42天内严重不良事件的发生情况。
在第1年和第2年确定了接种疫苗后10天内特定呼吸道和胃肠道症状的调整后比值比。流鼻涕或鼻塞、呕吐、肌肉疼痛和发热与第一剂CAIV-T显著相关。接种第二剂时，流鼻涕是与CAIV-T相关的唯一症状。在第2年，CAIV-T在任何特定呼吸道和胃肠道症状方面均未导致过量发生。在第3年和第4年，特定呼吸道和胃肠道症状与第2年观察到的情况相当。与CAIV-T相关的症状最有可能在接种第一剂疫苗的第2天出现。意外症状主要发生在胃肠道系统。约6%的CAIV-T接种者和3.6%的安慰剂接受者有胃肠道症状。CAIV-T似乎仅在接种第一剂疫苗时与腹痛和呕吐轻度过量相关。与安慰剂接受者相比，仅在CAIV-T接种者的第一剂疫苗中检测到镇痛药/退热药使用的统计学显著增加（23.5%对16.6%）。在第11至42天之间，使用CAIV-T与疾病、中耳炎或药物使用过量无关。在第1至4年的CAIV-T接种者中，6例严重不良事件均未归因于疫苗。
CAIV-T在儿童中是安全的。少数儿童出现了持续时间短的轻度呼吸道、胃肠道和全身症状，主要是在接种第一剂疫苗时。CAIV-T的连续年度剂量耐受性良好。
