Assessment of the anti-HBs antibody response in Beninese infants following 4 doses of HBV vaccine, including administration at birth, compared to the standard 3 doses regime; a cross-sectional survey

Abstract

Hepatitis B virus (HBV) infection remains one of the major neglected health issues worldwide. In sub-Saharan Africa (SSA), HBV endemicity is high, with more than 8% of the population being chronic HBV carriers. Recently, WHO recommended that all infants should receive their first dose of the HBV vaccine as soon as possible after birth. Unfortunately, the incorporation of a birth dose of HBV in the expanded programme immunization (EPI) has not occurred in the majority of countries in SSA. From April to September 2017, a cross-sectional survey was conducted in two vaccine units located in southern Benin. We assessed the sustained anti-HBs antibody response in infants induced by a standard scheme of 3 doses of HBV vaccination (6, 10, 14 weeks) in comparison to a scheme of 4 doses with a birth dose included (0, 6, 10, 14 weeks). Blood samples were systematically collected in the first 140 children aged 9 months and their mothers who had consented to participate for the detection of HBs antigen and the quantification of anti-HBs antibodies. The prevalence of HBV infection among infants and mothers was 2.2% and 7.1%, respectively. Infants who received 4 doses of HBV vaccine had a significantly higher level of anti-HBs antibody than those who received 3 doses of vaccine (557.9 UI/L vs. 386.9 UI/L, respectively, P = 0.03). We also showed that the scheme of 4 doses was associated with a significantly higher sustained protective response in comparison to the scheme of 3 doses (aOR 2.49, 95% CI 1.03–6.03, P = 0.04). This result provides further evidence of the importance of administering HBV vaccine at birth, but also highlights the importance for the prevention of vertical transmissions. Additional studies are needed to better establish the cost-effectiveness of such a 4 doses immunization strategy before implementing the HBV vaccination at birth in the EPI.

Introduction

Hepatitis B virus (HBV) infection is the most common chronic viral infection in man and remains a significant cause of morbidity and mortality worldwide [1]. An estimated one third of the world’s population is infected, and more than 350 million are chronic carriers of the virus [2]. In 2017, HBV resulted in 325 400 deaths, mostly due to complications such as cirrhosis and hepatocellular carcinoma [3]. The hepatitis B surface antigen (HBsAg) seroprevalence was 3.6% worldwide with the highest endemicity observed in countries of the African region (8.8%) [1]. Benin is one of the countries with the highest rates endemicity countries of HBV across sub-Saharan Africa (SSA), with over 1.4 million people infected [4] and a prevalence of HBV infection estimated at 16% [1].

The routine expanded programme on immunization (EPI) for Beninese neonates and infants includes many vaccine preventable diseases (Table 1). The latter included measles, diphtheria, pertussis, tetanus, polio, tuberculosis, hepatitis B, haemophilus influenza type b, pneumococcus and yellow fever. Vaccines included in the EPI are provided free of charge for parents due to financial support from the Beninese government through GAVI and UNICEF sponsorships. Women of reproductive age are also receive a tetanus toxoid booster immunization to protect their babies from tetanus.

Since perinatal or early postnatal transmission, particularly during infancy, is the major source of chronic HBV infection, World Health Organization (WHO) recommends that all infants should receive their first dose of the vaccine as soon as possible after birth, ideally within 24 h [5]. In most of SSA countries, including Benin, the initiation of the HBV birth vaccine dose has not yet been included in the national immunization program through the EPI. Although, some health centers do apply this recommendation, however the cost associated with the vaccine are met by the child’s parents and it is expensive (~8 USD per vaccine dose). In addition, little is known about the efficacy of administration of a birth vaccine dose in term of providing a sustained protection against HBV among Beninese infants, and data available on prevalence in Beninese infants and young children are particularly sparse.

The aim of the present study was to assess the efficacy of the scheme of 4 doses of HBV vaccine, with a first dose given at birth, in inducing a sustained protective response against HBV infection in comparison to the 3 doses traditionally given in the Beninese EPI to infants during the first months of life. Secondly, we determined the HBsAg prevalence among a vaccinated infant population. Lastly, we also separately evaluated the efficacy of the 4 doses scheme in infants born with a poor birth outcome such as small birthweight for gestational age (SGA), premature birth (PTB), and low birthweight (LBW).