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Hepatitis B virus (HBV) affects an estimated 1.5 million people globally each year, with nearly 296 million living with chronic infection, contributing significantly to cirrhosis, liver cancer, and premature mortality. Despite the availability of a highly effective vaccine, hepatitis B remains endemic in many low- and middle-income countries, including India, due to barriers in healthcare access and low vaccination uptake. While a timely birth dose prevents perinatal transmission, completion of the full vaccine schedule is essential to prevent horizontal transmission—a major mode of infection in India. India introduced the hepatitis B vaccine in select districts in 2002–2003 and scaled it nationally through the Universal Immunization Programme in 2011–2012.
This systematic review and meta-analysis aims to estimate the pooled coverage of hepatitis B vaccination among children under 5 years of age across different regions of India.
A comprehensive literature search will be conducted using PubMed, Embase, and CINAHL databases to identify studies published between 1 January 2000 and 30 May 2024. The search terms will include “Hepatitis B,” “vaccination coverage,” “children,” and “India,” combined using Boolean operators. Two independent reviewers will screen titles, abstracts, and full-text articles for eligibility. The AXIS tool will be used to assess the quality of cross-sectional studies. Pooled coverage rates will be estimated using a random-effects meta-analysis model. Heterogeneity will be assessed using the
Hepatitis B is a crucial global health concern, particularly in economically underdeveloped and developing countries such as India, where it significantly impacts public health. Hepatitis B virus (HBV) infection can progress to chronic hepatitis, cirrhosis, and liver cancer, making it a crucial target for preventive healthcare measures (
Despite the availability of effective vaccines, over 27 million children globally are not immunized against the essential doses of vaccinations (
National and regional averages mask significant diversity in HBV vaccine coverage across India. Of the 640 regions of India, 110 report coverage rates less than 40%. Notably, in 11 districts, primarily in the north region, less than 20% of children have been vaccinated against hepatitis B (
Understanding the current state of HBV coverage of vaccination among under-five children in India is crucial for identifying gaps and strategizing effective public health interventions (
What is the coverage of HBV vaccine uptake among under-five children in India?
This protocol was developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines (
The study protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the identifier CRD42024530478 (
Our systematic review will incorporate observational studies.
Primary research reports (original articles) reporting observational studies including cross-sectional, case–control, and cohort studies
Articles reporting hepatitis B vaccination coverage rates in under-five children in India
Reports available from National Immunization Programs in the public domain
Peer-reviewed articles and gray literature (such as government reports, policy documents, and unpublished theses) that provide sufficient and reliable data on hepatitis B vaccination coverage among under-five children in India
Qualitative studies, editorials, commentary, dissertations, conference proceedings, and reviews
Prospective SR study targets vaccine coverage among under-five children in India.
Children under the age of 5 years
Children vaccinated in India
This systematic review will encompass all studies carried out in hospital or clinical environments, including specialized hospital setups for HBV. We will include all publications up to the date of the search.
The basic search strategy will consist of three concepts: hepatitis B, vaccine coverage, and under-five children. The used for hepatitis B include “hepatitis b virus”[MeSH] OR “hepatitis-b”[MeSH] OR “hepatitis-b, chronic”[MeSH] OR “hepatitis-b surface antigens”[MeSH] OR “HBV infection”; for vaccine coverage, “Immunization”[MeSH Terms] OR “Vaccination”[MeSH Terms]; and for under-five children, “Children”[MeSH Terms] AND/OR “Under Five Children” AND/OR “Childhood” AND “India[Title/Abstract]”.
((“Hepatitis B”[MeSH Terms] OR “Hepatitis B virus”[MeSH Terms] OR “HBV infection” OR “hepatitis B” OR “chronic hepatitis B” OR “hepatitis B surface antigen” OR “HBsAg” OR “hepatitis-b”) AND (“Vaccination”[MeSH Terms] OR “Immunization”[MeSH Terms] OR “Vaccination Coverage”[MeSH Terms] OR “vaccine uptake” OR “vaccination rate” OR “immunization status” OR “birth dose” OR “dose completion”) AND (“Child, Preschool”[MeSH Terms] OR “Infant”[MeSH Terms] OR “Newborn”[MeSH Terms] OR “Children under five” OR “Under-five” OR “Childhood” OR “Infants” OR “Newborns” OR “Toddlers”) AND (“India”[MeSH Terms] OR India))
All three concepts will be added using AND, that is, #1 AND #2 AND #3.
Two reviewers will independently screen titles and abstracts to identify potentially eligible studies. The full texts of potentially eligible articles will be retrieved and assessed for inclusion by two additional researchers. Any disagreements during this stage will be resolved by a third reviewer with expertise in infectious diseases. A standardized data extraction form has been developed using Microsoft Excel. Data will be extracted from each study on variables such as sample size, sampling method, study design, study setting, sociodemographic characteristics, and hepatitis B vaccination coverage. Two reviewers will independently perform data extraction, and any discrepancies will be discussed and resolved through consensus.
Each included study will be independently evaluated by two reviewers to minimize bias. The risk of bias in observational studies will be evaluated using the Appraisal Tool for Cross-Sectional Studies (AXIS). This tool comprehensively evaluates studies based on 20 questions across five domains: background (1 question), materials and methods (10 questions), outcomes (5 questions), discussion (2 questions), and other characteristics (2 questions). Each domain will be assessed for risk of bias as either “Yes = 1” or “No/Don't Know = 0”. Studies scoring less than 50% will be categorized as highly biased, those scoring 51%–80% as moderately biased, and those scoring 81%–100% as low biased. For case–control and cohort studies, the Newcastle-Ottawa Scale (NOS) will be employed for quality assessment (
The information will be synthesized qualitatively based on the characteristics of the included studies. In addition, a meta-analysis will be conducted using the “metan” command in STATA 17.0 software (Stata Corp, TX, USA). Heterogeneity will be tested and reported using the
The analysis will be stratified by regions of India—east, west, north, south, central, and northeast—as well as by population characteristics, specifically tribal and non-tribal groups.
This systematic review and meta-analysis raises no ethical concerns, as it relies solely on published and non-commercial literature. Since individual patient data are not involved, there are no privacy issues. The findings will be submitted for publication in a peer-reviewed journal and may also be presented at a scientific conference.
No individuals were involved at any stage of this study protocol, as it constitutes only the review of existing published data.
This systematic review aims to summarize hepatitis B vaccination coverage among under-five children in India. There is an urgent need for an overall estimation of vaccine coverage of this disease as a step toward elimination. Effective vaccination not only prevents hepatitis B and its severe complications but also reduces the economic burden on the country. Reviewing existing data allows for the evaluation of the effectiveness of current vaccination programs and initiatives. This includes assessing the impact of past interventions and understanding which strategies have been successful or need modification. The evidence generated will support the planning, implementation, and modification of vaccination programs and will be valuable for awareness-building, resource allocation, and policy development. Moreover, the findings will be valuable for raising awareness, informing planning efforts, and guiding resource allocation. Following the protocol's quality standards, this systematic review aims to produce the most robust evidence possible. By compiling information on the clinical features and outcomes of hepatitis B, this review will enrich the currently limited data, offering fresh insights for healthcare professionals and researchers worldwide. The findings of this systematic review and meta-analysis may offer valuable insights for addressing gaps in the timely administration of the birth dose, particularly in rural and underserved areas. It may also inform strategies for improving outreach to under-immunized and high-risk populations, strengthening cold chain and vaccine logistics to minimize missed opportunities, and guiding the design of periodic catch-up campaigns for children who have missed routine doses.
Ethical approval is not required as the review is analyzing previously published data.
KD: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Resources, Writing – original draft, Writing – review & editing. AS: Investigation, Methodology, Project administration, Resources, Writing – review & editing. HB: Investigation, Methodology, Project administration, Resources, Writing – review & editing. YJ: Investigation, Methodology, Project administration, Resources, Writing – review & editing. DB: Investigation, Methodology, Project administration, Visualization, Writing – review & editing. SP: Conceptualization, Investigation, Methodology, Project administration, Resources, Writing – review & editing.
The authors declare that no financial support was received for the research and/or publication of this article.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors declare that no Generative AI was used in the creation of this manuscript.
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