MRC Centre for Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK.
Institut Pasteur, Université Paris Cité, Unité d'Épidémiologie des Maladies Émergentes, Paris, France.
Lancet Glob Health. 2023 May;11(5):e715-e728. doi: 10.1016/S2214-109X(23)00131-6.
Sub-Saharan Africa is highly endemic for hepatitis B virus (HBV); historically, most people were exposed during childhood through vertical or horizontal transmission. Although all African countries now provide a three-dose infant hepatitis B vaccination starting at age 6-8 weeks, only a third of African countries have introduced birth dose (HepB-BD) vaccine. Adding HepB-BD is fundamental to prevent vertical transmission, but its effectiveness in preventing horizontal transmission, compared with the three-dose infant vaccination alone, is unknown. We aimed to estimate the risk of early horizontal transmission in children of hepatitis B surface antigen (HBsAg)-negative mothers in sub-Saharan Africa stratified according to the vaccination schedule.
In this systematic review and meta-analysis we searched MEDLINE, Global Health, Embase, African Index Medicus and African Journals Online from their inception to Oct 24, 2022, for studies reporting HBsAg or HBV DNA, or both, in children (aged 0-5 years) of HBsAg-negative mothers. We excluded studies if children were only tested at birth. Two reviewers independently screened the titles and abstracts of all articles and data were extracted using a standardised pre-piloted data extraction sheet, and authors were contacted if any important information was missing. The primary outcome was the risk of HBV infection in children of HBsAg-negative mothers, stratified by vaccination schedule (no vaccination, first dose at 6-8 weeks, or first dose at birth). We pooled the child risks of HBsAg or HBV DNA-positivity from the age of 0 years to 5 years via a random-effect meta-analysis using a generalised linear mixed model. The study was registered on PROSPERO, CRD42021236203.
Of 8856 articles identified, 27 studies evaluating 10 003 children of HBsAg-negative mothers were included. The pooled risks of infection were 6·16% (95% CI 3·05-12·04; 155/1407) in the no vaccination group, 0·21% (0·04-1·15; 10/3425) in children who received their first dose at 6-8 weeks, and 0·05% (0·00-1·32; 3/2902) in children who received their first dose at birth. The difference was not statistically significant in children who received their first dose at 6-8 weeks and children who received their first dose at birth after adjusting for the study period, region, and maternal HIV status (test of moderators p=0·37).
In children of HBsAg-negative mothers, the risk of infection might be minimal even with the vaccination starting at 6-8 weeks, without clear additional benefit from HepB-BD. When births take place at home and timely administration of HepB-BD is challenging, antenatal HBsAg screening and selective HepB-BD might allow efficient allocation of resources to mother and child pairs at high risk compared with universal HepB-BD.
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For the French translation of the abstract see Supplementary Materials section.
撒哈拉以南非洲地区乙型肝炎病毒（HBV）流行率极高；历史上，大多数人都是在儿童时期通过垂直或水平传播感染的。尽管所有非洲国家现在都提供了从 6-8 周龄开始的三剂婴儿乙型肝炎疫苗接种，但只有三分之一的非洲国家引入了乙型肝炎母婴阻断（HepB-BD）疫苗。添加 HepB-BD 对于预防垂直传播至关重要，但与单独接种三剂婴儿疫苗相比，其预防水平传播的效果尚不清楚。我们旨在根据疫苗接种计划，估计撒哈拉以南非洲地区 HBsAg 阴性母亲的子女中早期水平传播的风险。
在本系统评价和荟萃分析中，我们检索了 MEDLINE、全球健康、Embase、非洲医学索引和非洲期刊在线，以获取自成立以来至 2022 年 10 月 24 日发表的报告 HBsAg 阴性母亲的儿童（年龄 0-5 岁）中 HBsAg 或 HBV DNA 或两者的研究。如果儿童仅在出生时接受检测，则排除研究。两名评审员独立筛选所有文章的标题和摘要，并使用标准化的预试验数据提取表提取数据，如果重要信息缺失，将联系作者。主要结局是根据疫苗接种计划（无接种、6-8 周龄时接种第一剂或出生时接种第一剂）分层的 HBsAg 阴性母亲的子女的 HBV 感染风险。我们通过使用广义线性混合模型的随机效应荟萃分析，汇总了 0 岁至 5 岁儿童的 HBsAg 或 HBV DNA 阳性率。该研究已在 PROSPERO 上注册，CRD42021236203。
在确定的 8856 篇文章中，有 27 项研究评估了 10003 名 HBsAg 阴性母亲的子女，纳入了研究。无接种组的感染风险为 6.16%（95%CI 3.05-12.04；155/1407），6-8 周龄时接种第一剂的儿童为 0.21%（0.04-1.15；10/3425），出生时接种第一剂的儿童为 0.05%（0.00-1.32；3/2902）。调整研究期间、地区和母亲 HIV 状况后，6-8 周龄时接种第一剂和出生时接种第一剂的儿童之间的差异无统计学意义（调整后检验调节剂的 p=0.37）。
在 HBsAg 阴性母亲的子女中，即使从 6-8 周龄开始接种疫苗，感染风险也可能很小，而且从 HepB-BD 中没有明显的额外获益。当分娩在家中进行且及时给予 HepB-BD 存在挑战时，产前 HBsAg 筛查和选择性 HepB-BD 可能允许与普遍给予 HepB-BD 相比，将资源有效地分配给高危母婴对。
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