Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial
Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial
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DOI：
10.1016/s0140-6736(05)71876-6
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发表时间：
2005-03-01
期刊：
影响因子：
168.9
通讯作者：
Adegbola, RA
中科院分区：
文献类型：
--
作者：
Cutts, FT;Zaman, SMA;Adegbola, RA
背景肺炎估计每年导致200万儿童死亡。肺炎链球菌是引起重症肺炎的最主要原因。我们的目标是评估九价肺炎球菌结合疫苗在儿童中的有效性。方法我们在冈比亚东部进行了一项随机、安慰剂对照的双盲试验。6-51周的儿童被随机分配三剂肺炎球菌结合疫苗(n=8718)或安慰剂(8719)，每剂间隔至少25天。我们的主要结果是首次出现放射性肺炎。次要终点为临床或严重临床肺炎、侵袭性肺炎球菌病和全因入院。分析是按照方案和治疗意图进行的。结果发现，529名分配了疫苗的儿童和568名分配了安慰剂的儿童没有包括在每种方案的分析中。按方案和意向处理分析的结果相似。通过按方案分析，接种疫苗的8189名儿童中有333名发生了放射性肺炎，相比之下，接受安慰剂的8151名儿童中有513名发生了放射性肺炎。肺炎球菌疫苗对首发放射性肺炎的有效率为37%(95%可信区间27-45)。临床肺炎首次发作总体减少7%(95%可信区间1-12)。该结合疫苗对疫苗血清型引起的侵袭性肺炎球菌病的有效率为77%(51-90)，对所有血清型引起的疾病的有效率为50%(21-69)，对全原因入院的有效率为15%(7-21)。我们还发现对死亡率的有效率为16%(3-28)。在接种肺炎球菌疫苗的儿童中发生了110起严重不良事件，而接受安慰剂的儿童中只有131例。在非洲农村，肺炎球菌结合疫苗对放射性肺炎和侵袭性肺炎球菌疾病有很高的疗效，可以大大减少入院人数，提高儿童存活率。应向非洲婴儿提供肺炎球菌结合疫苗。
Background Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children.Methods We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat.Findings 529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo.Interpretation In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.