A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection
A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection
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DOI：
10.1056/nejmoa035060
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发表时间：
2003-10-02
影响因子：
158.5
通讯作者：
Pierce, N
中科院分区：
文献类型：
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作者：
Klugman, KP;Madhi, SA;Pierce, N
背景：肺炎链球菌引起的急性呼吸道感染是幼儿发病和死亡的主要原因。我们在南非索韦托的一项随机双盲研究中评估了一种9价肺炎球菌结合疫苗的疗效。方法：在6、10和14周龄时，19,922名儿童接种了与白喉毒素非催化交叉反应突变体（CRM197）结合的9价肺炎球菌多糖疫苗，19,914名儿童接种了安慰剂。所有儿童均接种b型流感嗜血杆菌结合疫苗。根据意向治疗原则对疗效和安全性进行分析。结果：在未感染人类免疫缺陷病毒（HIV）的儿童中，由于疫苗中包含的血清型，该疫苗将侵袭性肺炎球菌疾病的首次发作发生率降低了83%（95%置信区间，39 - 97；对照组17例，疫苗接种者3例）。在感染艾滋病毒的儿童中，疗效为65%（95%置信区间，分别为24至86例；26例和9例）。在未感染艾滋病毒的儿童中，在意向治疗分析中，疫苗将放射学证实的肺泡实变首次发作的发生率降低了20%（95%置信区间，2至35例；对照组212例，接种疫苗组169例），在方案分析中（即在完全接种疫苗的儿童中），疫苗降低了25%（95%置信区间，4至41例，分别为158和119例）。耐青霉素菌株引起的侵袭性肺炎球菌病发病率降低了67%（95%置信区间，19至88例；对照组21例，接种疫苗组7例），耐甲氧苄啶-磺胺甲恶唑菌株引起的肺炎球菌病发病率降低了56%（95%置信区间，16至78例，分别为32例和14例）。结论：接种9价肺炎球菌结合疫苗可降低影像学确诊肺炎的发病率。该疫苗还降低了感染和未感染艾滋病毒的儿童中疫苗血清型和耐抗生素侵袭性肺炎球菌疾病的发病率。
BACKGROUND:Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children. We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a randomized, double-blind study in Soweto, South Africa.METHODS:At 6, 10, and 14 weeks of age, 19,922 children received the 9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197), and 19,914 received placebo. All children received Haemophilus influenzae type b conjugate vaccine. Efficacy and safety were analyzed according to the intention-to-treat principle.RESULTS:Among children without human immunodeficiency virus (HIV) infection, the vaccine reduced the incidence of a first episode of invasive pneumococcal disease due to serotypes included in the vaccine by 83 percent (95 percent confidence interval, 39 to 97; 17 cases among controls and 3 among vaccine recipients). Among HIV-infected children, the efficacy was 65 percent (95 percent confidence interval, 24 to 86; 26 and 9 cases, respectively). Among children without HIV infection, the vaccine reduced the incidence of first episodes of radiologically confirmed alveolar consolidation by 20 percent (95 percent confidence interval, 2 to 35; 212 cases in the control group and 169 in the vaccinated group) in the intention-to-treat analysis and by 25 percent (95 percent confidence interval, 4 to 41; 158 and 119 cases, respectively) in the per-protocol analysis (i.e., among fully vaccinated children). The incidence of invasive pneumococcal disease caused by penicillin-resistant strains was reduced by 67 percent (95 percent confidence interval, 19 to 88; 21 cases in the control group and 7 in the vaccinated group), and that caused by strains resistant to trimethoprim-sulfamethoxazole was reduced by 56 percent (95 percent confidence interval, 16 to 78; 32 and 14 cases, respectively).CONCLUSIONS:Vaccination with a 9-valent pneumococcal conjugate vaccine reduced the incidence of radiologically confirmed pneumonia. The vaccine also reduced the incidence of vaccine-serotype and antibiotic-resistant invasive pneumococcal disease among children with and those without HIV infection.