Immunogenicity of a Birth Dose of Hepatitis B Vaccine in Kinshasa, Democratic Republic of Congo: A Randomised, Controlled Trial.

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. Trial Registration: ClinicalTrials.gov identifier: NCT03897946.

Hepatitis B Virus Prevalence and Transmission in the Households of Pregnant Women in Kinshasa, Democratic Republic of Congo.

Background: The World Health Organization Africa region has high regional hepatitis B virus (HBV) prevalence, and evidence suggests more frequent horizontal HBV transmission than other regions. Context-specific epidemiological studies are needed to inform additional HBV prevention measures. Methods: In the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care in high-volume maternity clinics in Kinshasa, Democratic Republic of Congo. We recruited households of pregnant women ("index mothers") who were HBsAg-positive and HBsAg-negative, defining households as index-positive and index-negative, respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates. Results: We enrolled 1006 participants from 200 households (100 index-positive, 100 index-negative) across Kinshasa. HBsAg-positivity prevalence was more than twice as high in index-positive households (5.0% [95% confidence interval {CI}, 2.8%-7.1%]) as in index-negative households (1.9% [95% CI, .6%-3.2%]). HBsAg-positivity prevalence was 3.3 (95% CI, .9-11.8) times as high among direct offspring in index-positive versus index-negative households. 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 offspring in index-positive households. 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.

Changes in hepatitis B vaccine perception in response to the COVID-19 pandemic: Development of the Shift in vaccine confidence (SVC) survey tool.

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.

Participant perspectives to improve tenofovir adherence in the prevention of mother-to-child transmission of hepatitis B virus in Kinshasa, DRC.

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.

Hepatitis B virus prevalence and transmission in the households of pregnant women in Kinshasa, Democratic Republic of Congo.

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.

Low knowledge about hepatitis B prevention among pregnant women in Kinshasa, Democratic Republic of Congo.

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.