Neovac 2 Burkina Faso: Impact of the Integration of Hepatitis B Birth Dose Vaccine Into the Infant Immunization Schedule
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Study type: Interventional

Summary: 
      Hepatitis B virus (HBV) infection is an important global health problem, and the WHO adopted
      a strategy to eliminate HBV infection as a public health threat by the year 2030. In order to
      eliminate, it is critical to prevent the mother-to-child transmission (MTCT) of hepatitis B.
      Since 2009, the WHO recommends to administer hepatitis B vaccine within 24 hours of birth to
      prevent MTCT.2 However, in Africa, the majority of countries provide hepatitis B vaccine as a
      combined vaccine (pentavalent or hexavalent) at the age of 6-10-14 weeks or 8-12-16 weeks
      after the birth, and only 10 sub-Saharan African countries integrated birth dose vaccine into
      their national immunization program. This is because, the GAVI, the Vaccine Alliance, does
      not support monovalent hepatitis B vaccine, and also about half of babies in Africa are born
      at home without the immediate access to vaccination. Moreover, the evidence base to support
      this WHO's recommendation to start immunizing immediately at birth, rather than later at 6-8
      weeks of life, is not strong.

      Through a multidisciplinary approach comprising epidemiological, anthropological and economic
      components, the primary objective of the study is to measure the impact of the introduction
      of birth dose hepatitis B vaccine into the infant immunization program in Burkina Faso.

      Expected results will be to develop strong evidence base (effectiveness & cost-effectiveness)
      to recommend the integration of birth dose hepatitis B vaccine into the current vaccination
      schedule (8-12-16 weeks as a combined vaccine), to facilitate the Burkinabé Government to
      include the birth dose hepatitis B vaccine in their national vaccination program, to inform
      other African countries which have not yet integrated the birth dose hepatitis B vaccine in
      their national program and to imply whether additional strategy (e.g., maternal screening and
      antiviral therapy during pregnancy) might be necessary in order to eliminate the risk of
      mother-to-child transmission of hepatitis B.
    

Detailed description: 
      The study combines mixed methods to achieve its aim of evaluating the impact of the
      introduction of birth dose hepatitis B vaccine into the infant immunisation program in
      Burkina Faso. It is composed of 4 components:

      Workpackage (WP1): Stepped Wedge Cluster randomized controlled trial:

        -  to measure the impact of the introduction of birth dose hepatitis B vaccine into the
           infant immunization program on the mother-to-child transmission (primary objective)

        -  To examine a dose-dependent effect of hepatitis B vaccine (according to the total number
           of doses from one to four doses)

        -  To examine a time-dependent effect of the first dose of hepatitis B vaccine

        -  To study the impact of birth dose vaccine in infants aged at 9 months according to
           maternal HBsAg and HBeAg status

        -  To compare immunological responses in both groups by titration of anti-HBs antibodies in
           children at 9 months

        -  To describe vaccine coverage and its timeliness of birth dose hepatitis B vaccine and
           other routine infant vaccines in Burkina Faso

        -  To estimate the prevalence of HBV infection in mothers of 9-month-old children

      WP2: Anthropological study • To evaluate the acceptability of healthcare workers and people
      in the community about the integration of hepatitis B birth dose vaccine in the infant
      vaccination program in Burkina Faso

      WP3: Economic evaluation

        -  To evaluate the cost-effectiveness of the integration of hepatitis B birth dose vaccine
           in the infant vaccination program, compared to the conventional vaccine schedule
           (8-12-16 weeks) in Burkina Faso

        -  To evaluate the diagnostic performance of low-cost HBV markers to identify women at high
           risk of mother-to-child transmission in low-income countries

      WP4: Virological evaluation

      • To evaluate the diagnostic performance of low-cost HBV markers to identify women at high
      risk of mother-to-child transmission in low-income countries

      All the pregnant women attending the antenatal care in the rural health centres of two health
      districts (Dafra and Dô) in Hauts Bassins Region in Burkina Faso, and their infants will be
      asked to participate.

      Practical sequence of the cluster randomised trial. Even though the evidence is weak and the
      implementation has been suboptimal, the WHO currently recommends the universal administration
      of hepatitis B vaccine at birth. For this reason, a "stepped-wedge" design rather than a
      parallel group design has been selected. Of 24 rural health centers (Centre de santé et de
      promotion sociale : CSPS) in the districts of Dafra and Dô, introduce monovalent birth dose
      vaccine will be introduced in a phased manner on a centre by centre basis until all the 24
      CSPSs integrate the birth dose vaccines in the program. The rural area of these districts
      were selected given the proximity to our collaborative study center (Centre Muraz and AMP in
      Bobo Dioulasso). One of the 24 centers will be randomly selected as the first one to start
      integrating the birth dose in the program. Then, four weeks later, the second center will be
      randomly selected to start providing the birth dose vaccine. This will be continued until all
      24 CSPSs integrate birth dose vaccine in the program. At the end, this study design will
      generate two groups of infants in the study area during the study period: those born in
      centres which already implemented birth dose vaccine, and those born before the introduction
      of this vaccine.

      Informed consent will be obtained from pregnant women who visited routine antenatal care.
      Subsequently, babies born in a CSPS which is in the intervention period will receive birth
      dose vaccine whilst those born in a CSPS which is in the control period will not receive the
      birth dose. For those born at home in the intervention period will receive the monovalent
      hepatitis B vaccine at the first contact with CSPS, until 8 weeks after the birth when the
      first dose of pentavalent vaccine (DPT-Hib-HepB) is scheduled. All the infants, irrespective
      of study period, will receive three doses of pentavalent vaccine as scheduled in the national
      immunization program.

      Case report forms will be used (CRFs to collect basic demographic data of mothers and
      infants; time and place of birth; type of vaccines administered and its date Laboratory data:
      HBsAg for all infants and mothers; HBV DNA, HBeAg, AST/ALT for infants and mothers tested
      positive for HBsAg; anti-HBs for infants tested negative for HBsAg Paper CRFs filled by
      healthcare workers will be transferred to the study centre (AMP/Centre Muraz). The data will
      be entered independently by two operators to electronic database (RedCAP) that will be
      developed on the secured server of the Institut Pasteur.

      The risk of HBV infection (HBsAg-positivity) in infants at the age of 9 months between two
      groups will be compared using an intention-to-treat analysis, in order to assess the
      effectiveness of adding birth dose vaccine compared to the current vaccine schedule in
      preventing the mother-to-child transmission in Burkina Faso. To adjust for the calendar time
      and clustering in the data, A logistic regression model will fit with random effect for
      cluster and fixed effect for each step.
    

Intervention name(s): birth dose vaccination against hepatitis B strategy
Intervention type(s): Biological
Intervention description(s): Complex intervention targeting healthcare workers and involving:
training on hepatitis B awareness and management
training on EPI vaccination and cold chain
training on the modalities for the birth dose administration
the use of a monovalent unidose vaccine against Hepatitis B
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Pragmatic Stepped-wedge cluster randomized trial
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Infectious Disease Transmission, Vertical; immunization programs