Cervical cancer, caused by human papillomavirus (HPV), is almost entirely preventable through prophylactic HPV vaccination. Many countries have yet to implement HPV vaccination programmes or are struggling to achieve high vaccine coverage. This presents a major challenge for meeting the World Health Organisation (WHO) cervical cancer elimination target, with 90% of 15 year-old girls being vaccinated against HPV by 2030. Originally licenced as multidose vaccines, WHO has recently recommended that countries can offer a single HPV vaccine dose to 9-20 year olds. The IMPROVE-HPV consortium, a partnership of research institutions in Tanzania, Nigeria, UK and Spain, will investigate barriers to HPV vaccine uptake and the impact and acceptability of new HPV vaccine delivery strategies to improve vaccine coverage and effectiveness and reduce hesitancy. The consortium builds on previous successful collaborations in HPV epidemiology and vaccine research and qualitative research on barriers and facilitators to vaccine uptake. Tanzania has a multidose HPV vaccination programme in girls but will change to a single dose regimen in 2024. A gender-neutral HPV vaccination strategy is currently being implemented in Tanzania as part of a large cluster-randomised trial. Nigeria is one of the first countries to introduce national HPV vaccination with a single dose. Using these opportunities, IMPROVE-HPV will evaluate vaccine effectiveness, uptake and the factors affecting acceptability of (1) HPV two-dose vaccination delivery in females, (2) introducing or changing to a single dose vaccine regimen (3) gender-neutral HPV vaccination, and will also (4) investigate factors influencing vaccine hesitancy, community engagement and perceptions of HPV vaccines. The workplan directly addresses effectiveness and uptake of different HPV vaccine deployment strategies through phase IV/implementation research and will inform policy decision making in sub-Saharan Africa for HPV vaccination programmes.

This study proposes a major advance in research on intimate partner violence (IPV), a prominent public health and human rights issue. Worldwide, it is estimated that one in three women experience physical and/or sexual violence by a partner in their lifetime, with even higher rates reported in sub-Saharan Africa (WHO 2013). Cross-sectional surveys have documented the adverse health impacts of IPV and the factors that increase risk of female victimisation and male perpetration. Nonetheless, theoretical and programmatic development has stalled due to lack of clarity on the temporality of identified associations: do documented associations represent risk factors for violence or do they reflect the consequences of abuse? This deficit of understanding is especially pressing in low and middle income countries (LMICs) where few longitudinal cohort studies with IPV as an outcome exist. This study seeks to address this gap by following forward in time a cohort of 1200 Tanzanian women, using state of the art methods to measure violence, encourage disclosure and ensure participant safety. Both quantitative and qualitative data will be collected at 4 discrete time points over 5 years, making this the largest longitudinal study of IPV ever undertaken in the developing world. In addition, an in-depth study of 40 men and a cross-sectional survey of 600 men will be conducted. The goal of the research is to advance our understanding of the predictors and consequences of IPV to better inform the design of interventions to reduce violence in LMICs. Specifically the study aims to: 1) advance the theoretical frameworks of intimate partner violence; 2) investigate the temporality of key factors linked to IPV; 3) map the dynamics of partner violence over time; 4) and investigate pathways leading to intimate partner violence. This research is of immediate necessity to address a vital public health challenge of our time and has the strong potential to have a long lasting impact on shaping the research agenda on intimate partner violence.

Annually, almost 500,000 children under 5 years die from malaria in Africa. Timely access to effective antimalarial therapies is life saving as treatment with pre-referral rectal artesunate (RAS), followed by injectable artesunate and 3 days treatment with ACTs leads to an observed 96% reduction in mortality. Though recommended by the WHO for years, RAS deployment is very limited. The full treatment paradigm is not always feasible when access to primary healthcare facilities is limited due to lack of transport, non-availability of services, and cost. Rollout has recently been paused as outcomes data is incomplete in these contexts making the development of best practice recommendations challenging. Hence the relevance of the proposed study. The proposed project is an observational, non-inferiority study in Zambia and DRC. Community Health Care Workers will identify/diagnose, treat and follow up patients with (severe) malaria as part of integrated community case management. We will compare the efficacy of a treatment regimen consisting of pre-referral RAS, then post-referral injectable artesunate, followed by three days of ACT versus a regimen consisting of RAS alone followed by three days of ACT in remote areas. We will compare recurrence rate between the two regimens at Day 28, the number of lives saved, the risk of generating drug resistance. We will assess and mitigate operational and institutional facilitators and barriers in all stakeholders (patients, caregivers, health care providers, regulators, malaria experts) and recommend sustainable policies for this remote context. This generated evidence will support policy development and implementation. The proposed consortium brings together vital experience in the rollout and deployment of rectal artesunate, study design and execution, social science, data collection and management, stakeholder engagement and translation of research results into clinical practice.

Diabetes Mellitus (DM) contributes to an estimated 11.3% of adult deaths worldwide. Approximately 1 in 10 adults globally are estimated to have DM and the prevalence will rise significantly over the coming decades, especially in sub-Saharan Africa. People with DM have a three-fold increased risk of developing TB, and two-fold higher risk of dying from TB or experiencing treatment failure or recurrent disease, further threatening global TB control. As such, the growing burden of DM alongside the continuing TB epidemic have huge health and socio- economic impact. PROTID performs the first randomized controlled trial (RCT) globally to evaluate efficacy, safety, cost-utility and population impact of preventive treatment of TB preventive therapy for people with DM. It also examines gaps in diagnosis and management of DM and DM-TB in Uganda and Tanzania. Our results will guide global policy on TB prevention and management in people with DM, and this can have large socio-economic impact. In Africa, this is highly relevant given the double burden of DM and TB. In Europe, our results will be highly relevant for migrants and people living in eastern Europe, as both groups have a high burden of DM, latent tuberculosis infection (LTBI) and TB disease. PROTID’s results so far, and other advancements in the field, have already set clear research priorities beyond PROTID. PROTID is very well-positioned to take these forward, with strengthened leadership and research capacity in PROTID’s African partners embedded in a global research network, and its accumulated data on the largest and most-well characterized longitudinal cohort on DM and TB globally.

Diabetes is a common co-morbidity among people living with HIV. Since Oct 2021, we have been conducting a phase III randomised placebo-controlled trial of metformin among people living with HIV and pre-diabetes in Dar es Salaam, Tanzania (EDCTP RIA2018CO-2513). The aim is to test whether metformin can prevent progression to diabetes among people living with HIV. The primary endpoint is the time to diabetes. We had planned to enrol 2100 participants, follow-up for 3 years, and finish at the end of Dec 2024. COVID-19 resulted in severe delays to regulatory review. HIV care was decentralised away from health facilities to community posts to reduce COVID-19 risk, which led to much slower recruitment. We have now enrolled 1550 participants over the last 20 months. Less than 1% have been lost to follow-up. We will reach our target recruitment in Dec 2023 and will continue follow-up until Dec 2025. This will provide an average follow-up of 3 years per participant. Analyses of aggregated data to date show that glucose levels and weight have fallen over first 12 months among the trial cohort. Thus, we believe that trial will answer the research question by continuing follow-up until Dec 2025. In 2026, we will disseminate the findings to stakeholders and to the international bodies. We are collecting clinical, health economics, and qualitative data. The trial is being done as an equitable partnership between European and African researchers, and in partnership with Ministry of Health policy-makers and African patient representative bodies. We have good links with the African Centres for Disease Control, World Health Organisation (WHO-AFRO and Geneva offices), and Global Fund in order to inform policy considerations. Merck Pharma has provided medicinal products including the placebo.