Despite the policy recommendation and effectiveness of administering the hepatitis B birth-dose vaccine (HepB-BD) to newborns to prevent mother-to-child hepatitis B transmission, timely uptake remains an issue. Countries adopting the HepB-BD to their national immunization schedule report programmatic challenges to administering the vaccine within the recommended 24-hour window after delivery. Further, while the World Health Organization recommends streamlining three birth-dose vaccines (HepB-BD, BCG, and OPV0), scarce Sub-Saharan(SSA)-based literature reports on a streamlined and timely approach to birth-dose vaccines. As more SSA countries adopt the new birth-dose vaccine to their immunization schedules, a systematically developed implementation strategy-Vaccination of Newborns-Innovative Strategies to Hasten Birth-Dose vaccines' delivery (VANISH-BD)-will facilitate the adoption and implementation of timely birth-dose vaccine uptake. In this paper, we describe the development of the implementation strategy using intervention mapping, an evidence-based and theory-driven approach. We report on the development of our intervention, beginning with the needs assessment based in Kinshasa Province, Democratic Republic of the Congo (DRC), informing step 1 of intervention mapping. The intervention is contextually relevant, locally produced, sustainable, and designed to improve timely birth-dose vaccine uptake in the DRC. We intend to inform future implementers about improving timely and streamlined birth-dose vaccine uptake and for VANISH-BD to be adapted for similar contexts.

The WHO recommends hepatitis B birth-dose vaccination (HepB-BD), but it is not routinely given in most sub-Saharan African countries. We aimed to assess the immunogenicity of HepB-BD in addition to the existing hepatitis B vaccine (HepB3) schedule in Kinshasa, Democratic Republic of Congo among HBV-unexposed and HBV-exposed infants. Using an open-label, randomised, controlled design, HBV-unexposed infants were randomised (1:1) to receive the standard HepB3 vaccine series (group U3), or to receive HepB-BD in addition to HepB3 (group U4). A supplemental cohort of HBV-exposed infants (group E4) received HepB-BD and HepB3. We compared the proportion of infants with protective antibodies against HBV (HBV surface antibody >= 10 mIU/mL) between groups U3 and U4 and groups U4 and E4 at 12 months of age. Between August 20 and October 9, 2019, we enrolled 281 mother/infant dyads; 88 (31.3%) returned at 12 months. Most infants had protective antibodies against HBV at 12 months: 92.9% (75.7%-98.2%) in group U3, 85.7% (67.5%-94.5%) in group U4 and 96.9% (95% CI: 81.2%-99.6%) in group E4. Trends held in estimates adjusted for loss-to-follow-up (LTFU) and baseline imbalance across groups. In this first randomised trial assessing the addition of HepB-BD to the hepatitis B vaccine schedule in SSA, we found that HBV-unexposed infants who received the 3-dose and 4-dose vaccine series had similar immunogenicity against HBV at 12 months. A high proportion of infants, and notably HBV-exposed infants, had protective antibodies. Though extrapolation of findings may be limited by LTFU, this study adds real-world evidence regarding HepB-BD implementation in sub-Saharan Africa.

Hepatitis B virus (HBV) antiviral administration and adherence are essential to reach the World Health Organization's 2030 hepatitis elimination goals. As HBV treatment guidelines are now simplified and expanded, adherence to treatment will be critical, but challenges to adherence are poorly studied. After introducing tenofovir disoproxil fumarate (TDF) monotherapy to expectant mothers with high-risk HBV in Kinshasa, DRC, we conducted semi-structured interviews to understand medication adherence behaviors, to complement pill counts and measurement of TDF metabolite levels. Key facilitators of adherence identified included trust in healthcare workers, a better understanding of HBV, and family support. Identified barriers included fear of stigma and low health literacy. Knowledge about HBV disease remains low, underscoring the importance of ongoing education of clinic staff and patients alike.

The COVID-19 pandemic has disrupted access to, adherence to, and perceptions of routine vaccinations. We developed the Shift in Vaccine Confidence (SVC) survey tool to assess the impact of the pandemic on routine vaccinations, with a focus on the HBV vaccine, in Kinshasa, Democratic Republic of Congo (DRC). This study describes the content validation steps we conducted to ensure the survey tool is meaningful to measure changes in vaccine confidence to regular immunization (HBV vaccine) due to the pandemic. Three rounds of stakeholder feedback from a DRC-based study team, content and measurement experts, and study participants allowed us to produce a measure with improved readability and clarity.

Prevention of mother-to-child transmission (PMTCT) programs for hepatitis B virus (HBV) are critical to reach the World Health Organization's 2030 HBV elimination goals. Despite demonstrated feasibility utilizing HIV infrastructure, HBV PMTCT programs are not implemented in many African settings, including in the Democratic Republic of Congo (DRC). In a previous pilot of HBV PMTCT implementation in DRC's capital, Kinshasa, we observed low TDF metabolite levels at delivery among women with high-risk HBV who were given tenofovir disoproxil fumarate (TDF) antiviral therapy. As such, we conducted qualitative interviews with women who received TDF to understand facilitators and barriers of medication adherence. We used a modified Information-Motivation-Behavioral Skills model (IMB+) as a framework for thematic content analysis. We found that trust in healthcare workers, familial support, and improved awareness of the disease and treatment options were important facilitators of TDF adherence; pill size, social stigma, and low HBV knowledge were barriers to adherence. While overall acceptance of TDF was high in this pilot, improved TDF adherence is needed in order to reach efficacious levels for preventing transmission from mothers to newborns. We suggest ongoing HBV sensitization within existing maternity and HIV care infrastructure would address gaps in knowledge and stigma identified here. Additionally, given the trust women have towards maternity center staff and volunteers, scaled HBV PMTCT interventions should include specific sensitization and education for healthcare affiliates, who currently receive no HBV prevention or information in DRC. This study is timely as TDF, particularly future long-acting formulations, could be considered as an alternate rather than adjuvant to birth-dose vaccination for HBV PMTCT in sub-Saharan Africa.

Background Despite global efforts to reduce preventable childhood illness by distributing infant vaccines, immunization coverage in sub-Saharan African settings remains low. Further, timely administration of vaccines at birth—tuberculosis (Bacille Calmette–Guérin [BCG]) and polio (OPV0)—remains inconsistent. As countries such as Democratic Republic of the Congo (DRC) prepare to add yet another birth-dose vaccine to their immunization schedule, this study aims to improve current and future birth-dose immunization coverage by understanding the determinants of infants receiving vaccinations within the national timeframe. Methods The study used two ordered regression models to assess barriers to timely BCG and first round of the hepatitis B (HepB3) immunization series across multiple time points using the Andersen Behavioral Model to conceptualize determinants at various levels. The assessment leveraged survey data collected during a continuous quality improvement study (NCT03048669) conducted in 105 maternity centers throughout Kinshasa Province, DRC. The final sample included 2398 (BCG analysis) and 2268 (HepB3 analysis) women-infant dyads living with HIV. Results Between 2016 and 2020, 1981 infants (82.6%) received the BCG vaccine, and 1551 (68.4%) received the first dose of HepB3 vaccine. Of those who received the BCG vaccine, 26.3%, 43.5%, and 12.8% received BCG within 24 h, between one and seven days, and between one and 14 weeks, respectively. Of infants who received the HepB3 vaccine, 22.4% received it within six weeks, and 46% between six and 14 weeks of life. Many factors were positively associated with BCG uptake, including higher maternal education, household wealth, higher facility general readiness score, and religious-affiliated facility ownership. The factors influencing HepB3 uptake included older maternal age, higher education level, household wealth, transport by taxi to a facility, higher facility general and immunization readiness scores, and religious-affiliated facility ownership. Conclusions This study demonstrated that the study participants’ uptake of vaccines was consistent with the country average, but not in a timely manner. Various factors were associated with timely uptake of BCG and HepB3 vaccines. These findings suggest that investment to strengthen the vaccine delivery system might improve timely vaccine uptake and equity in vaccine coverage.

Background Despite routine infant vaccination and blood donor screening, the Democratic Republic of Congo (DRC) has high hepatitis B virus (HBV) prevalence compared to the United States and Europe. Through the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we characterized household prevalence in DRC’s capital, Kinshasa, to inform additional prevention efforts. Methods We introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care (ANC) in high-volume maternity clinics in Kinshasa. We recruited households of pregnant women who were HBsAg-positive and HBsAg-negative, defining households as “exposed” and “unexposed,” respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results We enrolled 1,006 participants from 200 households (100 exposed, 100 unexposed) across Kinshasa. HBsAg prevalence was more than twice as high in exposed households (5.0%; 95% CI: 2.8%-7.1%) as in unexposed households (1.9%; 0.6%-3.2%). Exposed direct offspring had 3.3 (0.9, 11.8) times the prevalence of unexposed direct offspring. Factors associated with HBsAg-positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among exposed offspring. Conclusions Vertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.

Background National vaccine policies across the world have successfully improved infant vaccine coverage, but birth-dose (BD) vaccine coverage remains low. Countries such as the Democratic Republic of the Congo (DRC) aim to include the hepatitis B birth-dose (HepB-BD) vaccine in their national immunization schedule. HepB-BD’s short window for administration – within 24 hours of delivery to prevent mother-to-child transmission – adds to the complexity of streamlined and timely BD vaccines. This study aims to identify and understand barriers and facilitators to timely delivery of BD vaccine in Kinshasa Province, DRC, through individuals’ accounts with different perspectives on the uptake of the BD vaccine in preparation for its future roll-out. Methods We conducted semi-structured interviews in seven health facilities across Kinshasa Province from June to July 2021. We purposefully sampled health facilities from the provinces’ five most prominent facility types—private, public, Catholic, Protestant, and not-for-profit. We interviewed decision-makers and/or providers from various levels of the health care continuum, including midwives, immunization staff, heads of maternity and immunizations, and vaccine officials at the health zone and the Programme Elargi de Vaccination (PEV) to understand administrative barriers to BD vaccines. We also conducted interviews with expectant mothers to elicit knowledge and perceptions about infant vaccines. Results We interviewed 30 participants (16 informants and 14 expectant mothers). Interviewees were recruited from 7 health facilities, 2 health zones, and PEV. Data analysis was guided by the Consolidated Framework for Implementation Research (CFIR). Our analysis identified 13 constructs (2-3 per domain) related to the success of timely and streamlined BD vaccines. We found significant barriers within and across each domain; most notably, the multi-dose vials of existing BD vaccines determining when facility staff could vaccinate newborns, often resulting in untimely vaccinations; logistical concerns with regular national vaccine stockouts and ability to store vaccines; complex and unsynchronized vaccine fees across facilities; inadequate communication across delivery and vaccination wards; and limited and at times incorrect understanding of vaccines among mothers and other community members. Conclusions Using the CFIR framework, this study integrated perspectives from facility informants and expectant mothers to inform national policy and implementation of the HepB-BD in DRC. These stakeholder-driven findings should guide the streamlining of timely BD vaccinations upon HepB-BD implementation.

Abstract Background: Hepatitis B virus (HBV) remains a leading infectious cause of death worldwide, and is highly prevalent in Sub-Saharan Africa (SSA). The prevention of mother-to-child transmission (PMTCT) programs for HBV are critical to reaching elimination targets and utilizing existing HIV testing and treatment infrastructure. Building on a feasibility study to introduce tenofovir disoproxil fumarate antiviral therapy to pregnant women with high-risk HBV in the Democratic Republic of the Congo (DRC), we examine the social and psychological facilitators of medication adherence of women who participated in this HBV PMTCT program.Methods: This study utilizes a qualitative exploratory approach involving women in Kinshasa, DRC who were identified as high-risk HBV during pregnancy and completed the pilot tenofovir antiviral program. Six participants were identified and completed in-depth, open-ended phone interviews. This study adopts a modified Information-Motivation-Behavioral Skills model (IMB+) to identify emerging themes related to tenofovir adherence.Results: A strong trust in healthcare workers, family support, and improved awareness of the disease and treatment options through enrollment in the PMTCT program facilitated tenofovir adherence. Barriers to medication adherence included social stigma and low healthcare literacy specific to HBV.Conclusions: Our study highlights the feasibility of medication adherence in HBV PMTCT programs in a low-resource setting and the importance of incorporating initiatives that address hepatitis B stigma and other social barriers. These findings are relevant to future HBV PMTCT scale-up, which is needed in the DRC and in similar African contexts with high HBV prevalence. Trial registration: The parent study was registered with clinicaltrials.gov under identifier NCT03567382. Date of registration: 25/06/2018

Background: Despite global efforts to reduce preventable childhood illness by distributing infant vaccines, immunization coverage in sub-Saharan African settings remains low. Further, timely administration of vaccines at birth – tuberculosis (Bacille Calmette-Guérin [BCG]) and polio (OPV0) – remains inconsistent. Countries such as Democratic Republic of the Congo (DRC) prepare to add yet another birth-dose vaccine in their immunization schedule, but research is necessary to understand the determinants of current birth-dose vaccines’ timely administration. This study aims to improve current and future birth-dose immunization coverage by understanding determinants of infants receiving vaccinations within the national timeframe. Methods: The study used two ordered regression models to assess barriers to timely BCG and first round of hepatitis B (HepB3) immunization across multiple time points using the Andersen Behavioral Model to conceptualize determinants at various levels. The assessment leveraged survey data collected during a continuous quality improvement study (NCT03048669) conducted in 105 maternity centers throughout Kinshasa Province, DRC. The final sample included 2,398 (BCG analysis) and 2,268 (HepB3 analysis) women-infant dyads living with HIV. Results: Between 2016 and 2020, 1,981 infants (82.6%) received the BCG vaccine, and 1,551 (68.4%) received the first dose of HepB3 vaccine. Of those who received the BCG vaccine, 26.3, 43.5%, and 12.8% received BCG within 24 hours, between one and seven days, and between one and 14 weeks, respectively. Of infants who received the HepB3 vaccine, 22.4% received it within six weeks, and 46% between six and 14 weeks of life. Many factors were positively associated with BCG uptake, including higher maternal education, household wealth, higher facility general readiness score, and religious-affiliated facility ownership. The factors influencing HepB3 uptake included older maternal age, higher education level, household wealth, transport by taxi to a facility, higher facility general and immunization readiness scores, and religious-affiliated facility ownership. Conclusion: This study demonstrated that the study participants’ uptake of vaccines was consistent with the country average, but not in a timely manner. Various factors were associated with timely uptake of BCG and HepB3 vaccines. These findings suggest that investment to strengthen the vaccine delivery system might improve timely vaccine uptake and equity in vaccine coverage.

Infants infected perinatally with hepatitis B (HBV) are at the highest risk of developing chronic hepatitis and associated sequelae. Prevention of mother-to-child transmission (PMTCT) of HBV requires improved screening and awareness of the disease. This study evaluated existing HBV knowledge among pregnant mothers (n = 280) enrolled in two HBV studies in urban maternity centers in Kinshasa, Democratic Republic of the Congo. All mothers responded to three knowledge questions upon study enrollment. Baseline levels of knowledge related to HBV transmission, treatment, prevention, and symptoms were low across all participants: 68.8% did not know how HBV was transmitted, 70.7% did not know how to prevent or treat HBV MTCT, and 79.6% did not know signs and symptoms of HBV. Over half of participants responded “I don’t know” to all questions. HBV-positive women who participated in both studies (n = 46) were asked the same questions during both studies and showed improved knowledge after screening and treatment, despite no formal educational component in either study (p < 0.001). These findings highlight the need for intensified education initiatives in highly endemic areas to improve PMTCT efforts.

Summary Background Hepatitis B virus (HBV) remains endemic throughout sub-Saharan Africa despite the widespread availability of effective childhood vaccines. In the Democratic Republic of the Congo, HBV treatment and birth-dose vaccination programmes are not established. We, therefore, aimed to evaluate the feasibility and acceptability of adding HBV testing and treatment of pregnant women as well as the birth-dose vaccination of HBV-exposed infants to the HIV prevention of mother-to-child transmission programme infrastructure in the Democratic Republic of the Congo. Methods We did a feasibility study in two maternity centres in Kinshasa: Binza and Kingasani. Using the already established HIV prevention of mother-to-child transmission programme at these two maternity centres, we screened pregnant women for HBV infection at routine prenatal care registration. Those who tested positive and had a gestational age of 24 weeks or less were included in this study. Eligible pregnant women with a high viral load (≥200 000 IU/mL or HBeAg positivity, or both) were considered as having HBV of high risk of mother-to-child transmission and initiated on oral tenofovir disoproxil fumarate (300 mg/day) between 28 weeks and 32 weeks of gestation and continued through 12 weeks post partum. All HBV-exposed infants received a birth-dose of monovalent HBV vaccine (Euvax-B Pediatric: Sanofi Pasteur, Seoul, South Korea; 0·5 mL) within 24 h of life. All women were followed up for 24 weeks post partum, when they completed an exit questionnaire that assessed the acceptability of study procedures. The primary outcomes were the feasibility of screening pregnant women to identify those at high risk for HBV mother-to-child transmission and to provide them with antiviral prophylaxis, the feasibility of administrating the birth-dose vaccine to exposed infants, and the acceptability of this prevention programme. This study is registered with ClinicalTrials.gov, NCT03567382. Findings Between Sept 24, 2018, and Feb 22, 2019, 4016 women were approached and screened. Of these pregnant women, 109 (2·7%) were positive for HBsAg. Of the 109 women, 91 (83%) met the eligibility criteria for participation. However, only data from 90 women—excluding one woman who had a false pregnancy—were included in the study analysis. The median overall age of the enrolled women was 31 years (IQR 25–34) and the median overall gestational age was 19 weeks (15–22). Ten (11%) of 91 women evaluated had high-risk HBV infection. Nine (90%) of the ten pregnant women with high-risk HBV infection received tenofovir disoproxil fumarate and one (10%) refused therapy and withdrew from the study; five (56%) of the nine women achieved viral suppression (ie, <200 000 IU/mL) on tenofovir disoproxil fumarate therapy by the time of delivery and the remaining four (44%) had decreased viral loads from enrolment to delivery. A total of 88 infants were born to the 90 enrolled women. Of the 88 infants, 60 (68%) received a birth-dose vaccine; of these, 46 (77%) received a timely birth-dose vaccine. No cases of HBV mother-to-child transmission were observed. No serious adverse events associated with tenofovir disoproxil fumarate nor with the birth-dose vaccine were reported. Only one (11%) of nine women reported dizziness during the course of tenofovir disoproxil fumarate therapy. The study procedures were considered highly acceptable (>80%) among mothers. Interpretation Adding HBV screening and treatment of pregnant women and infant birth-dose vaccination to existing HIV prevention of mother-to-child transmission platforms is feasible in countries such as the Democratic Republic of the Congo. Birth-dose vaccination against HBV infection integrated within the current Expanded Programme on Immunisation and HIV prevention of mother-to-child transmission programme could accelerate progress toward HBV elimination in Africa. Funding Gillings Innovation Laboratory award and the National Institutes of Health. Translations For the French and Lingala translations of the abstract see Supplementary Materials section.

ABSTRACTBackgroundHepatitis B virus (HBV) remains endemic throughout sub-Saharan Africa despite the widespread availability of effective vaccines. We evaluated the feasibility of adding HBV testing and treatment of pregnant women and birth-dose vaccination of HBV-exposed infants to the HIV prevention of MTCT (PMTCT) program infrastructure in the Democratic Republic of the Congo (DRC), where HBV treatment and birth-dose vaccination programs are not established.MethodsAs part of the HIV PMTCT program at two maternity centers in Kinshasa, DRC, pregnant women were screened for HBV at routine prenatal care registration. Pregnant women with high viral load and/or HBeAg positivity were offered tenofovir disoproxil fumarate (TDF). HBV-exposed infants received a birth-dose of HBV vaccine within 24 hours of life. The primary endpoint was the feasibility and acceptability of the study.FindingsOf 4,016 women screened, 109 (2.7%) were HBsAg-positive. Ten of 91 (11.1%) women evaluated had high-risk disease. Of 88 infants, 60 (68.2%) received a birth-dose vaccine; of these, 46 (76.7%) received a timely birth-dose. No cases of HBV MTCT were observed in our cohort. There were no serious adverse events associated with TDF nor with birth-dose vaccine. The study procedures were highly acceptable (>80%) among mothers.InterpretationAdding HBV screening and treatment of pregnant women and infant birth-dose vaccination to existing HIV PMTCT platforms is feasible in countries like the DRC. Birth-dose vaccination against HBV integrated within the current Expanded Programme on Immunization (EPI) and HIV PMTCT program could accelerate progress toward HBV elimination in Africa.