Klugman Keith P, Madhi Shabir A, Huebner Robin E, Kohberger Robert, Mbelle Nontombi, Pierce Nathaniel
Medical Research Council, University of the Witwatersrand, National Institute for Communicable Diseases, Respiratory and Meningeal Pathogens Research Unit, Johannesburg, South Africa.
N Engl J Med. 2003 Oct 2;349(14):1341-8. doi: 10.1056/NEJMoa035060.
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.
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.
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).
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.
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。我们在南非索韦托进行了一项随机双盲研究，评估了9价肺炎球菌结合疫苗的疗效。
19922名儿童在6周、10周和14周龄时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，19914名儿童接受了安慰剂。所有儿童均接种了b型流感嗜血杆菌结合疫苗。根据意向性分析原则对疗效和安全性进行分析。
在未感染人类免疫缺陷病毒（HIV）的儿童中，该疫苗使疫苗所含血清型引起的侵袭性肺炎球菌病首次发作的发生率降低了83%（95%置信区间为39%至97%；对照组17例，疫苗接种组3例）。在感染HIV的儿童中，疗效为65%（95%置信区间为24%至86%；分别为26例和9例）。在未感染HIV的儿童中，在意向性分析中，该疫苗使放射学确诊的肺泡实变首次发作的发生率降低了20%（95%置信区间为2%至35%；对照组212例，接种疫苗组169例），在符合方案分析中（即完全接种疫苗的儿童中）降低了25%（95%置信区间为4%至41%；分别为158例和119例）。青霉素耐药菌株引起的侵袭性肺炎球菌病的发生率降低了67%（95%置信区间为19%至88%；对照组21例，接种疫苗组7例），甲氧苄啶-磺胺甲恶唑耐药菌株引起的发生率降低了56%（95%置信区间为16%至78%；分别为32例和14例）。
接种9价肺炎球菌结合疫苗可降低放射学确诊肺炎的发生率。该疫苗还降低了感染HIV和未感染HIV儿童中疫苗血清型和抗生素耐药侵袭性肺炎球菌病的发生率。
