Middleton Bianca F, Fathima Parveen, Snelling Thomas L, Morris Peter
Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia.
Health and Clinical Analytics, School of Public Health, University of Sydney, New South Wales, Australia.
EClinicalMedicine. 2022 Oct 6;54:101687. doi: 10.1016/j.eclinm.2022.101687. eCollection 2022 Dec.
Oral rotavirus vaccines have lower effectiveness in high child mortality settings. We evaluated the impact of additional dose(s) schedules of rotavirus vaccine on vaccine immunogenicity and reduction in episodes of gastroenteritis.
We searched Medline (via PubMed), Cochrane databases and ClinicalTrials.gov for randomised controlled trials from 1973 to February 2022, evaluating the immunological and clinical impact of additional dose vs standard dose oral rotavirus vaccine schedules. We extracted immunogenicity - proportion of children with evidence of anti-rotavirus IgA seroresponse, and clinical - proportion of children with at least one episode of severe rotavirus gastroenteritis, outcome data and used random effects meta-analysis where appropriate. We assessed the methodological quality of the studies using the Cochrane risk of bias tool. The study protocol was registered in PROSPERO (CRD42021261058).
We screened 536 items and included 7 clinical trials. Our results suggest moderate to high level evidence that an additional dose rotavirus vaccine schedule improves IgA vaccine immune response, including additional doses administered as a booster dose schedule >6 months old; IgA vaccine seroresponse 74·3% additional dose schedule vs 56·1% standard dose schedule RR 1·3 (95%CI, 1·15 - 1·48), and when administered to children who were seronegative at baseline; IgA vaccine seroresponse 48.2% additional dose schedule vs 29.6% standard dose schedule RR 1.86 (95%CI 1.27 to 2.72). Only one study evaluated reduction in gastroenteritis episodes and found little benefit in first year of life, 1·8% vs 2·0% RR 0·88 (95% CI, 0·52 to 1·48), or second year of life, 1·7% vs 2·9% RR 0·62 (95%CI, 0·31 - 1·23).
Administering an additional dose of oral rotavirus vaccines is likely to result in an improved vaccine immune response, including when administered as a booster dose to older children. Evidence of an impact on diarrhoeal disease is needed before additional dose rotavirus vaccine schedules can be recommended as vaccine policy.
BM was funded by the National Health and Medical Research Council, the Royal Australasian College of Physicians Paediatrics and Child Health Division, and the Australian Academy of Science.
口服轮状病毒疫苗在儿童死亡率高的地区有效性较低。我们评估了额外剂量的轮状病毒疫苗接种方案对疫苗免疫原性及减少肠胃炎发作次数的影响。
我们检索了Medline（通过PubMed）、Cochrane数据库和ClinicalTrials.gov，以查找1973年至2022年2月期间的随机对照试验，评估额外剂量与标准剂量口服轮状病毒疫苗接种方案的免疫和临床影响。我们提取了免疫原性——有抗轮状病毒IgA血清反应证据的儿童比例，以及临床指标——至少有一次严重轮状病毒肠胃炎发作的儿童比例、结局数据，并在适当情况下使用随机效应荟萃分析。我们使用Cochrane偏倚风险工具评估研究的方法学质量。该研究方案已在PROSPERO（CRD42021261058）注册。
我们筛选了536项研究，纳入了7项临床试验。我们的结果表明，有中等到高水平的证据表明，额外剂量的轮状病毒疫苗接种方案可改善IgA疫苗免疫反应，包括在6个月以上儿童中作为加强剂量接种额外剂量；额外剂量接种方案的IgA疫苗血清反应率为74.3%，而标准剂量接种方案为56.1%，相对风险（RR）为1.3（95%置信区间[CI]，1.15 - 1.48），以及在基线时血清阴性的儿童中接种；额外剂量接种方案的IgA疫苗血清反应率为48.2%，而标准剂量接种方案为29.6%，RR为1.86（95%CI为1.27至2.72）。只有一项研究评估了肠胃炎发作次数的减少情况，发现对1岁儿童益处不大，分别为1.8%对2.0%，RR为0.88（95%CI，0.52至1.48），对2岁儿童也如此，分别为1.7%对2.9%，RR为0.62（95%CI，0.31 - 1.23）。
额外接种一剂口服轮状病毒疫苗可能会改善疫苗免疫反应，包括对大龄儿童作为加强剂量接种时。在额外剂量的轮状病毒疫苗接种方案可被推荐作为疫苗政策之前，需要有对腹泻病有影响的证据。
BM由澳大利亚国家卫生与医学研究委员会、皇家澳大利亚内科医师学院儿科学与儿童健康部以及澳大利亚科学院资助。
