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尽管在喀麦隆及时进行了出生时疫苗接种,但乙型肝炎病毒母婴传播的残余风险(ANRS 12303):一项单中心、纵向观察性研究。

Residual risk of mother-to-child transmission of hepatitis B virus infection despite timely birth-dose vaccination in Cameroon (ANRS 12303): a single-centre, longitudinal observational study.

机构信息

Unité d'Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France.

Laboratoire de Virologie, CHU Angers, Laboratoire HIFIH, Angers Université, Angers, France.

出版信息

Lancet Glob Health. 2022 Apr;10(4):e521-e529. doi: 10.1016/S2214-109X(22)00026-2. Epub 2022 Feb 17.

Abstract

BACKGROUND

In sub-Saharan Africa, administration of hepatitis B virus (HBV) birth-dose vaccines remains suboptimal. Evidence is scarce on whether African countries should focus on increasing vaccine coverage or developing strategies incorporating additional measures, such as peripartum antiviral prophylaxis to pregnant women at high risk. To better inform decision makers, we estimated the residual risk of mother-to-child transmission despite HBV birth-dose vaccine in Cameroon.

METHODS

We did a single-centre, longitudinal observational study. Pregnant women were systematically screened for HBV surface antigen (HBsAg) at Tokombéré District Hospital (Tokombéré district, Cameroon). Children born to HBsAg-positive mothers in 2009-16 who received the HBV birth-dose vaccine and three subsequent doses of pentavalent vaccine at 6, 10, and 14 weeks were followed up prospectively in 2015-17. In children, capillary blood was obtained for HBsAg rapid test and dried blood spots to quantify HBV DNA concentrations. Venous blood was also collected from HBsAg-positive children. Mother-to-child transmission was confirmed by whole-genome sequencing.

FINDINGS

Between Jan 31, 2009, and Dec 31, 2016, 22 243 (66·8%) of 33 309 pregnant women accepted antenatal HBV screening, of whom 3901 (17·5%) were HBsAg positive. 2004 (51·4%) of 3901 children who were born to HBsAg-positive mothers received the HBV birth-dose vaccine, of whom 1800 (89·8%) also completed the three-dose pentavalent vaccine. In total, the current analysis included 607 children who had a follow-up serosurvey. The prevalence of HBsAg was 5·6% in children who received the birth-dose vaccine in less than 24 h, 7·0% in those who received it 24-47 h after birth, and 16·7% in those who received it 48-96 h after birth (p=0·083). 35 (89·7%) of 39 infected children were born to mothers positive for HBV e antigen with high HBV DNA of 5·3 log IU/mL or more. Whole-genome sequencing of HBV in infected mother-child pairs confirmed high identity proportions of 99·97-100%.

INTERPRETATION

We documented a substantial risk of mother-to-child transmission despite timely administration of the HBV birth-dose vaccine within 24 h after birth. To reach WHO's elimination targets, peripartum antiviral prophylaxis might be required in parts of Africa, in addition to increasing coverage of the HBV birth-dose vaccine.

FUNDING

Agence nationale de recherches sur le sida et les hépatites virales (ANRS).

摘要

背景

在撒哈拉以南非洲,乙型肝炎病毒 (HBV) 基础免疫接种的实施情况仍不理想。对于非洲国家是应专注于提高疫苗覆盖率,还是应制定包含额外措施的策略,例如为高风险孕妇提供围产期抗病毒预防,目前尚缺乏相关证据。为了更好地为决策者提供信息,我们在喀麦隆估计了 HBV 基础免疫接种后母婴传播的残余风险。

方法

我们开展了一项单中心、纵向观察性研究。在托孔贝雷区医院(喀麦隆托孔贝雷区),对所有孕妇进行乙型肝炎表面抗原 (HBsAg) 筛查。2009 年至 2016 年期间,HBsAg 阳性母亲所生的儿童接受了 HBV 基础免疫接种,并在 6、10 和 14 周时接种了后续的 3 剂五联疫苗,我们于 2015 年至 2017 年对这些儿童进行了前瞻性随访。在儿童中,采集毛细血管血进行 HBsAg 快速检测和干血斑检测以定量 HBV DNA 浓度。同时也从 HBsAg 阳性儿童中采集静脉血。通过全基因组测序来确定母婴传播。

发现

2009 年 1 月 31 日至 2016 年 12 月 31 日期间,共有 33309 名孕妇接受了乙肝病毒产前筛查,其中 3901 名(17.5%)为 HBsAg 阳性。3901 名 HBsAg 阳性母亲所生的 2004 名(51.4%)儿童接受了 HBV 基础免疫接种,其中 1800 名(89.8%)还完成了 3 剂五联疫苗接种。总的来说,本次分析纳入了 607 名接受了随访血清学调查的儿童。在出生后 24 h 内接种疫苗的儿童中,HBsAg 阳性率为 5.6%,在出生后 24-47 h 接种疫苗的儿童中为 7.0%,在出生后 48-96 h 接种疫苗的儿童中为 16.7%(p=0.083)。35 名(89.7%)感染儿童的母亲为 HBV e 抗原阳性,HBV DNA 水平>5.3 log IU/mL。对感染母婴对的 HBV 进行全基因组测序证实了 99.97%-100%的高同源性比例。

解释

尽管在出生后 24 h 内及时接种了 HBV 基础免疫疫苗,但我们仍发现母婴传播存在较大风险。为了达到世卫组织的消除目标,除了提高 HBV 基础免疫接种覆盖率之外,在非洲部分地区可能还需要进行围产期抗病毒预防。

资助

国家艾滋病和病毒性肝炎研究署(ANRS)。

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