干预措施以提高口服疫苗的效果：系统评价和荟萃分析。
Interventions to improve oral vaccine performance: a systematic review and meta-analysis.
机构信息
Centre for Genomics & Child Health, Blizard Institute, Queen Mary University of London, London, UK; Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
Department of Infectious Disease Epidemiology, St Mary's Campus, Imperial College London, London, UK.
出版信息
Lancet Infect Dis. 2019 Feb;19(2):203-214. doi: 10.1016/S1473-3099(18)30602-9. Epub 2019 Jan 30.
BACKGROUND
Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance is uncertain.
METHODS
We did a systematic review and meta-analysis of interventions designed to increase oral vaccine efficacy or immunogenicity. We searched Ovid-MEDLINE and Embase for trials published until Oct 23, 2017. Inclusion criteria for meta-analysis were two or more studies per intervention category and available seroconversion data. We did random-effects meta-analyses to produce summary relative risk (RR) estimates. This study is registered with PROSPERO (CRD42017060608).
FINDINGS
Of 2843 studies identified, 87 were eligible for qualitative synthesis and 66 for meta-analysis. 22 different interventions were assessed for oral poliovirus vaccine (OPV), oral rotavirus vaccine (RVV), oral cholera vaccine (OCV), and oral typhoid vaccines. There was generally high heterogeneity. Seroconversion to RVV was significantly increased by delaying the first RVV dose by 4 weeks (RR 1·37, 95% CI 1·16-1·62) and OPV seroconversion was increased with monovalent or bivalent OPV compared with trivalent OPV (RR 1·51, 95% CI 1·20-1·91). There was some evidence that separating RVV and OPV increased RVV seroconversion (RR 1·21, 95% CI 1·00-1·47) and that higher vaccine inoculum improved OCV seroconversion (RR 1·12, 95% CI 1·00-1·26). There was no evidence of effect for anthelmintics, antibiotics, probiotics, zinc, vitamin A, withholding breastfeeding, extra doses, or vaccine buffering.
INTERPRETATION
Most strategies did not improve oral vaccine performance. Delaying RVV and reducing OPV valence should be considered within immunisation programmes to reduce global enteric disease. New strategies to address the gap in oral vaccine efficacy are urgently required.
FUNDING
Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and WHO Polio Research Committee.
背景
与高收入国家相比，口服疫苗在中低收入国家的效果较差。干预措施是否能提高口服疫苗的效果尚不确定。
方法
我们对旨在提高口服疫苗效力或免疫原性的干预措施进行了系统评价和荟萃分析。我们在 Ovid-MEDLINE 和 Embase 中检索了截至 2017 年 10 月 23 日发表的试验。荟萃分析的纳入标准为每个干预类别有 2 项或 2 项以上的研究和可获得的血清转化率数据。我们进行了随机效应荟萃分析，以产生汇总相对风险（RR）估计值。本研究已在 PROSPERO（CRD42017060608）注册。
结果
在 2843 项研究中，有 87 项研究适合定性综合分析，66 项研究适合荟萃分析。对口服脊髓灰质炎疫苗（OPV）、口服轮状病毒疫苗（RVV）、口服霍乱疫苗（OCV）和口服伤寒疫苗进行了 22 种不同干预措施的评估。通常存在高度异质性。RVV 首剂推迟 4 周可显著提高 RVV 血清转化率（RR 1.37，95%CI 1.16-1.62），单价或双价 OPV 与三价 OPV 相比可提高 OPV 血清转化率（RR 1.51，95%CI 1.20-1.91）。有一些证据表明，将 RVV 和 OPV 分开接种可提高 RVV 血清转化率（RR 1.21，95%CI 1.00-1.47），提高疫苗接种剂量可提高 OCV 血清转化率（RR 1.12，95%CI 1.00-1.26）。驱虫药、抗生素、益生菌、锌、维生素 A、母乳喂养、额外剂量或疫苗缓冲剂均无效果。
结论
大多数策略并未改善口服疫苗的效果。在免疫规划中，应考虑推迟 RVV 接种和减少 OPV 价数，以减少全球肠道疾病。急需新的策略来解决口服疫苗效力方面的差距。
资金来源
惠康信托基金会、比尔及梅林达·盖茨基金会、英国医学研究理事会和世界卫生组织脊髓灰质炎研究委员会。
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