Graves P, Gelband H
Dept of Preventive Medicine & Biometrics, University of Colorado Health Sciences Center, Box C 245, 4200 E Ninth Ave, Denver, CO 80262, USA.
Cochrane Database Syst Rev. 2000(2):CD000129. doi: 10.1002/14651858.CD000129.
Despite continued efforts to control the disease, malaria remains a major health problem in many regions of the world, especially sub-Saharan Africa, and new ways to control or eradicate the disease are urgently needed. Two types of vaccine, SPf66 vaccine against the asexual stages, and NANP vaccines against the sporozoite stages of the Plasmodium parasite, have been tested in randomised clinical trials in endemic areas.
To assess the effects of malaria vaccines.
The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Organisations and researchers in the field were contacted.
Randomised trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale, and placebo.
Two independent reviewers assessed trial quality and conducted data extraction.
Thirteen efficacy trials involving about 7700 people were included. There were nine trials of the Spf66 vaccine and four trials of the NANP vaccines. There was large heterogeneity between trials when investigating the effect of SPf66 in reducing incidence of the first attack of P. falciparum malaria. When trials were subcategorised by location, there was no evidence for effect of SPf66 in reducing incidence of P. falciparum in four African trials conducted in children under 5 years of age (Peto odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.81 to 1.14). In five trials outside Africa with participants aged 2 years to adult, there was a reduction in incidence by SPf66 vaccine (Peto OR = 0.77, 95% CI 0.67 to 0.88, fixed effects model). Significant heterogeneity remained between trials conducted outside Africa. Using a random effects model for these five trials, the OR was 0.74 (95% CI 0.54 to 1.01). In five trials, there was no evidence for effect of the SPf66 vaccine on the incidence of the first attack of P. vivax malaria (OR 1.01, 95% CI 0.87 to 1.17). Trials to date have not indicated any severe adverse effects of SPf66 vaccine. In three trials of NANP-based vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (OR 1.12, 95% CI 0.64 to 1.93).
REVIEWER'S CONCLUSIONS: There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America may be justified. Trials to date have not been of sufficient size to evaluate the effect of malaria vaccines on mortality or on severe malaria requiring admission to hospital. There was not enough evidence to evaluate the use of NANP vaccines.
尽管一直在努力控制疟疾，但它在世界许多地区，尤其是撒哈拉以南非洲地区，仍然是一个主要的健康问题，因此迫切需要控制或根除该疾病的新方法。两种类型的疫苗，即针对疟原虫无性阶段的SPf66疫苗和针对疟原虫子孢子阶段的NANP疫苗，已在流行地区进行了随机临床试验。
评估疟疾疫苗的效果。
检索了Cochrane传染病组试验注册库、Cochrane对照试验注册库、Medline、Embase以及文章的参考文献列表。还联系了该领域的组织和研究人员。
比较针对恶性疟原虫、间日疟原虫、三日疟原虫或卵形疟原虫的疫苗与安慰剂的随机试验。
两名独立的审阅者评估试验质量并进行数据提取。
纳入了13项涉及约7700人的疗效试验。其中有9项关于SPf66疫苗的试验和4项关于NANP疫苗的试验。在研究SPf66降低恶性疟原虫疟疾首次发作发生率的效果时，各试验之间存在很大的异质性。当按地点对试验进行亚分类时，在4项针对5岁以下儿童在非洲进行的试验中，没有证据表明SPf66能降低恶性疟原虫的发生率（Peto比值比[OR]=0.96，95%置信区间[CI]为0.81至1.14）。在5项非洲以外地区针对2岁至成年人的试验中，SPf66疫苗降低了发病率（Peto OR=0.77，95%CI为0.67至0.88，固定效应模型）。非洲以外地区进行的试验之间仍存在显著的异质性。对这5项试验使用随机效应模型，OR为0.74（95%CI为0.54至1.01）。在5项试验中，没有证据表明SPf66疫苗对间日疟原虫疟疾首次发作的发生率有影响（OR为1.01，95%CI为0.87至1.17）。迄今为止的试验未表明SPf66疫苗有任何严重不良反应。在3项基于NANP的疫苗试验中，没有证据表明这些疫苗能预防恶性疟原虫疟疾（OR为1.12，95%CI为0.64至1.93）。
没有证据表明SPf66疫苗在非洲能预防恶性疟原虫。在其他地区，接种SPf66疫苗后恶性疟原虫疟疾发作略有减少。在南美洲对SPf66疫苗进行进一步研究可能是合理的。迄今为止的试验规模不足以评估疟疾疫苗对死亡率或对需要住院治疗的严重疟疾的影响。没有足够的证据来评估NANP疫苗的使用情况。
