Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.
Lancet Infect Dis. 2021 Aug;21(8):1161-1174. doi: 10.1016/S1473-3099(20)30693-9. Epub 2021 Apr 30.
Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV (fIPV) administration is one of the strategies to ensure IPV availability. We reviewed studies comparing the effects of fractional with full-dose IPV vaccination to determine when seroconversion proportions with each strategy become similar in children aged 5 years and younger.
In this systematic review and meta-analysis, we searched 16 databases in July, 2019, for trials and observational studies, including ongoing studies that compare immunogenicity and adverse events of fractional-dose (0·1 mL) to full-dose (0·5 mL) IPV in healthy children aged 5 years or younger regardless of study design, number of doses, and route of administration. Screening, selection of articles, data extraction, and risk of bias assessment were done in duplicate, and conflicts were resolved by discussion or arbitration by a third author. We assessed immunogenicity, the main outcome, as proportion of seroconverted participants and changes in geometric mean titres of anti-poliovirus antibodies. Timepoints were eligible for analysis if measurements were done at least 4 weeks after vaccination. Summary estimates were pooled by use of random-effects meta-analysis. Analysis was stratified by study design, type of outcome measure, type of poliovirus, and number of doses given. We assessed heterogeneity using the χ test of homogeneity and quantified it using the I statistic. We assessed risk of bias using the Cochrane risk of bias tool, and the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The study is registered with PROSPERO, CRD42018092647.
860 records were screened for eligibility, of which 36 potentially eligible full-text articles were assessed and 14 articles were included in the final analysis: two ongoing trials and 12 articles reporting on ten completed studies. For poliovirus type 2, there were no significant differences in the proportions of seroconversions between fractional and full doses of IPV for two or three doses: the risk ratio for serconversion at one dose was 0·61 (95% CI 0·51-0·72), at two doses was 0·90 (0·82-1·00), and at three doses was 0·95 (0·91-1·00). Geometric mean titres (GMTs) for poliovirus type 2 were lower for fIPV than for full-dose IPV: -0·51 (95% CI -0·87 to -0·14) at one dose, -0·49 (-0·70 to -0·28) at two doses, and -0·98 (-1·46 to -0·51) at three doses. The seroconversion meta-analysis for the three-dose comparison was homogeneous (p=0·45; I=0%), whereas heterogeneity was observed in the two-dose (p<0·00001; I=88%) and one-dose (p=0·0004; I=74%) comparisons. Heterogeneity was observed in meta-analyses of GMTs for one-dose (p<0·00001; I=92%), two-dose (p=0·002; I=80%), and three-dose (p<0·00001; I=93%) comparisons. Findings for types 1 and 3 were similar to those for type 2. The certainty of the evidence was high for the three-dose comparisons and moderate for the rest of the comparisons.
There is no substantial difference in seroconversion between three doses of fIPV and three doses of full-dose IPV, although the full dose gives higher titres of antibodies for poliovirus type 1, 2, and 3. Use of fractional IPV instead of the full dose can stretch supplies and possibly lower the cost of vaccination.
South African Medical Research Council and the National Research Foundation of South Africa.
自从世界卫生组织（WHO）建议在常规免疫计划中至少引入一剂灭活脊髓灰质炎病毒疫苗（IPV）以来，全球一直存在 IPV 短缺。使用小剂量 IPV（fIPV）接种是确保 IPV 供应的策略之一。我们综述了比较 fIPV 与全剂量 IPV 接种效果的研究，以确定在 5 岁以下儿童中，两种策略的血清转化率何时变得相似。
在这项系统综述和荟萃分析中，我们于 2019 年 7 月检索了 16 个数据库，以寻找比较健康 5 岁及以下儿童使用小剂量（0.1 mL）和全剂量（0.5 mL）IPV 的免疫原性和不良事件的试验和观察性研究，包括正在进行的研究，无论研究设计、剂量数和给药途径如何。筛选、文章选择、数据提取和偏倚风险评估均由两名作者进行，如有冲突则通过讨论或由第三名作者仲裁解决。我们评估了免疫原性这一主要结局，其指标为血清转化率和抗脊髓灰质炎病毒抗体几何平均滴度的变化。如果接种后至少 4 周进行了测量，则该时间点可进行分析。汇总估计值通过随机效应荟萃分析进行合并。分析按研究设计、结局测量类型、脊髓灰质炎病毒类型和接种剂量数进行分层。我们使用 χ 检验同质和 I 统计量衡量异质性。我们使用 Cochrane 偏倚风险工具评估偏倚风险，并使用 Grading of Recommendations Assessment，Development and Evaluation 方法评估证据的确定性。该研究在 PROSPERO 注册，CRD42018092647。
筛选出 860 条记录以确定其是否符合纳入标准，其中有 36 篇潜在的全文文章进行了评估，最终有 14 篇文章纳入了最终分析：两项正在进行的试验和 12 篇报告了 10 项完成研究的文章。对于脊髓灰质炎病毒 2 型，两剂或三剂 fIPV 与全剂量 IPV 的血清转化率无显著差异：一剂时血清转化率的风险比为 0.61（95%CI 0.51-0.72），两剂时为 0.90（0.82-1.00），三剂时为 0.95（0.91-1.00）。fIPV 的脊髓灰质炎病毒 2 型几何平均滴度（GMT）低于全剂量 IPV：一剂时为-0.51（95%CI-0.87 至-0.14），两剂时为-0.49（-0.70 至-0.28），三剂时为-0.98（-1.46 至-0.51）。三剂比较的血清转化率荟萃分析结果具有同质性（p=0.45；I=0%），而两剂（p<0.00001；I=88%）和一剂（p=0.0004；I=74%）比较的结果则具有异质性。一剂（p<0.00001；I=92%）、两剂（p=0.002；I=80%）和三剂（p<0.00001；I=93%）比较的 GMT 荟萃分析结果均存在异质性。1 型和 3 型的结果与 2 型相似。三剂比较的证据确定性为高，其余比较的证据确定性为中。
虽然全剂量 IPV 可产生更高的脊髓灰质炎病毒 1、2 和 3 型抗体滴度，但 3 剂 fIPV 与 3 剂全剂量 IPV 之间的血清转化率并无显著差异。使用小剂量 IPV 代替全剂量可延长供应，并可能降低疫苗接种成本。
南非医学研究理事会和南非国家研究基金会。
