A Simplified screen-and-Treat-all prOphylaxis approach in Pregnant women to stop Hepatitis B Virus mother-to-child transmission in Malawi and The Gambia (STOP-HBV)

Research question: Is a simplified “screen-and-treat all” intervention for pregnant women living with hepatitis B virus (HBV) infection an effective, feasible, acceptable, safe and cost-effective policy to stop mother-to-child transmission (MTCT) of HBV in Malawi and The Gambia? Background: HBV is the principal cause of cirrhosis and liver cancer in Africa. Elimination of HBV as a public health threat can only be achieved by preventing MTCT, as the most important route of new infections. Over two thirds of all new infections globally occur in Africa, due to limited implementation of interventions to prevent MTCT. In addition to infant HBV vaccination, the World Health Organisation (WHO) recommends screening all pregnant women for HBV and administering tenofovir antiviral therapy for women with viral load (VL) =200,000 IU/ml or positive HBeAg. A key barrier to implementation of these effective interventions in Africa is a lack of access to these diagnostic tests. As a pragmatic response, since March 2024, the WHO has recommended where tests are unavailable to treat all HBsAg-positive pregnant irrespective of VL, but there is currently no available evidence to support this policy. Aims & objectives: This study aims to assess the real-world effectiveness, feasibility, acceptability, safety and cost-effectiveness of a novel simplified HBV “screen-and-treat all” prophylaxis strategy in pregnant women to prevent HBV MTCT in Malawi and The Gambia. We will assess i. the effectiveness of implementation measured by acceptance of HBV testing (target >90%), uptake of tenofovir treatment (target >90%) and infant HBV transmission at 6 months of age, aiming to achieve the WHO elimination target of <2% of HBV MTCT, ii. the socio-cultural and health system facilitators and barriers to successful implementation, iii. the maternal and neonatal safety including monitoring for maternal flares following cessation of tenofovir treatment, and iv. the cost-effectiveness and impact of the intervention toward HBV elimination targets. The study will strengthen the capacity to conduct world-leading research in Malawi and The Gambia. Methods: This is a single-arm non-randomized pragmatic implementation study. The study will be carried out in rural antenatal services in The Gambia, in collaboration with the MRC Unit The Gambia (MRCG) and in Malawi in collaboration with the Malawi Liverpool Wellcome Programme (MLW), both Ministries of Health (MOH) and involvement of community and patient group representatives. The study will recruit 658 HBsAg-positive pregnant women (329/country). HBV MTCT will be defined by the proportion of HBsAg-positive infants tested at 6 months of age. Timelines for delivery: The project will be delivered over 48 months, via 4 work-packages. Anticipated impact & dissemination: Through extensive engagement with women, community members, patient representative organisations, policy makers at MOH, the World Hepatitis Alliance (WHA) and the WHO, we expect a significant impact on health policy across Africa. Patients and community groups will be central to the project implementation and adaptation to ensure that the proposed strategy will have the best chance of sustainable implementation. Through training and mentorship of local staff and research fellows, we will increase awareness and confidence in preventing HBV infection and enhance research capacity. We will work closely with the WHO and WHA to disseminate the findings and lessons learnt.