NIHRDataInsights/HRCSData huggingface dataset:
Title: Effects of metronidazole plus intermittent preventive treatment of malaria in pregnancy on birth outcomes: a randomised controlled trial in Zambia
Funder: Medical Research Council

Abstract: Current interventions in sub-Saharan Africa to reduce the burden of malaria infection and curable sexually transmitted and reproductive tract infections (STIs/RTIs) in pregnancy are inadequate. To protect against adverse pregnancy outcomes in malaria-endemic areas, the World Health Organization (WHO) recommends the provision of intermittent preventive treatment of malaria (IPTp) in pregnancy using sulphadoxine-pyrimethamine (SP). However, the loss of parasite sensitivity to SP has compromised this intervention. The WHO recommends the syndromic management of curable STIs/RTIs in low- and middle-income countries. Bacterial vaginosis (BV) and Trichomonas vaginalis (TV) are included in these guidelines. However, syndromic management fails to detect the majority of infections in women. Metronidazole (MTZ), safe during the second and third trimester of pregnancy, is curative of TV and inhibits recurrence of BV. IPTp using dihydroartemisinin-piperaquine (DP) is the leading candidate to replace IPTp-SP. A trial in Kenya showed that IPTp-DP was superior to IPTp-SP in preventing malaria-related endpoints. However, IPTp-SP was superior to IPTp-DP in reducing the incidence of low birth weight, small-for-gestational age, and preterm birth. A potential explanation is that IPTp-SP also protects against non-malarial causes of adverse pregnancy outcomes. Thus, we propose a three-arm trial that will compare SP plus MTZ placebo versus SP plus MTZ versus DP plus MTZ in a geographic area of north-east Zambia where malaria transmission is high, malaria parasite-resistance to SP is high, and the prevalence of BV and TV in pregnant women is also high. We will conduct cost-effectiveness analyses and discrete choice experiments, as well as two sub-studies that are key to interpreting results from the main trial and understanding microbiological mechanics of chemoprevention against adverse birth outcomes and antimicrobial resistance.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION;6.1 PHARMACEUTICALS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Antenatal Couples' Counselling in Uganda (ACCU)
Funder: Medical Research Council

Abstract: About 28% of married women and 32% of unmarried women in Uganda have an unmet need for family planning; 43% do not deliver in a health facility. This is linked to high rates of maternal, perinatal and neonatal mortality. Delivery in a health facility is a window of opportunity for providing long-acting reversible contraception (LARC), specifically the contraceptive implant or intra-uterine device (IUD), in the immediate post-partum period prior to discharge. Although health workers have been trained to provide the post-partum IUD, uptake remains low because women need to get the approval of their husbands, who are usually absent at the time of delivery. Men also need to agree the place of delivery as women rely on them for transport and/or money to access a health facility. Yet men rarely accompany their partners to antenatal clinics so couples do not often discuss these issues. Qualitative interviews with Ugandans suggested that antenatal couples' counselling could be a possible solution. Focus groups agreed with this idea, an explained that men do not often attend antenatal clinics because they work during the week and feel treated rudely. Our proposed intervention aims to overcome these barriers by providing initial counselling in couples' homes by community health workers, known as village health teams (VHTs), who will encourage couples to attend antenatal clinics together. The clinics will screen health education films, incorporating feedback from local focus groups. Health workers will be trained in communication skills and couples' counselling, as well as refresher training on providing postpartum contraception. We will pilot this intervention to see how well it can be delivered. We will also test the feasibility of conducting a cluster-randomised trial of the intervention. In particular we will evaluate whether VHTs can recruit and follow up pregnant women in their villages, and whether they are able to use smartphones to collect and enter data.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Efficacy and safety of chlorhexidine cleansing in reducing bacterial skin colonisation of hospitalised low birthweight neonates:a pilot trial (NeoCHG)
Funder: Medical Research Council

Abstract: This is a pilot randomised study, with a factorial design, comparing the efficacy and safety of varying regimens of skin application of chlorhexidine wipes to low birth weight hospitalised neonates. Comparison will be made between different concentrations of chlorhexidine, and different frequencies of application, as well as addition or omission of emollient, and against a control group. Efficacy will primarily be measured as reduction of total and pathogen specific bacterial colony forming units (CFUs) on a pooled skin swab of the cervical skin folds, umbilicus, nose and groin, as well as a separate peri-rectal swab. Safety, which is the other co-primary outcome, will be based on a modified newborn skin score which assesses skin condition. Other secondary end points will include the change in proportions of bacterial species in different groups, as well as other adverse events such as hypothermia, and skin reactions requiring discontinuation of chlorhexidine. Chlorhexidine will be applied to the skin of low birth weight neonates (1-2kg) from day 2 of life onwards (sparing the face), and in varying concentrations (0.5%, 1% and 2%), either daily (Monday-Friday) or three times a week (Monday, Wednesday, Friday), and with or without emollient application. Skin swabs will be collected at regular intervals, before chlorhexidine application, and then after 3, 7, and 14 days (or on discharge if earlier). The factorial design, including a control group, enables efficient comparison of frequency, concentration, and emollient in one trial. This will then inform the choice of a regimen to be taken forward into a future trial of chlorhexidine skin application as part of a bundle of interventions aiming to reduce neonatal sepsis and all-cause mortality.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Intermittent preventive treatment with dihydroartemisinin-piperaquine: a new malaria strategy to prevent adverse birth outcomes in Papua, Indonesia
Funder: Medical Research Council

Abstract: Malaria in pregnancy is a major cause of maternal and neonatal death in Papua, Indonesia. In our recent trial in Papua we showed that monthly intermittent preventive treatment (IPTp) with the long-acting artemisinin-based combination dihydroartemisinin-piperaquine (DP) among pregnant women in the second and third trimester protected with long-lasting insecticide-treated nets was safe, tolerable and efficacious compared to the current policy of single screening at ANC booking and treatment of RDT-positive cases. The Ministry of Health (MOH) Indonesia now plans to pilot the strategy in the routine health system in Papua, Indonesia. This study will assess the programme effectiveness of IPTp-DP delivery through antenatal care services and women's adherence to the monthly 3-day DP treatment regimen in a 'real life' setting. The study will be undertaken in nine community health centres in the lowlands and their associated health posts in Timika city. In the first 18 months, we will support MOH to implement the intervention using quality improvement (QI) approaches to continuously strengthen service delivery, uptake and adherence through plan-do-study-act cycles. We will also support the MoH to collect safety data for pharmacovigilance. A mixed-methods evaluation will be conducted towards the end of the pilot using exit interviews to assess delivery effectiveness, home visits to assess adherence, and qualitative research to explore provider perceptions of the drivers of successful integration, scalability and user acceptability. The primary outcome is adherence and delivery effectiveness, defined as the proportion of pregnant women who receive the first dose of IPTp-DP by DOT at ANC and have the correct number of DP tablets for subsequent doses on exit, and when visited at home have verified they completed the course. We will also determine cost-effectiveness compared to current policy and the cost of implementing IPTp-DP from the provider (MOH) perspective.


Research activity codes: 6.1 PHARMACEUTICALS;8.2 HEALTH AND WELFARE ECONOMICS;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: An implementation trial of continuous quality improvement for antenatal syphilis and HIV detection and treatment in Indonesia: The MENJAGA study
Funder: Medical Research Council

Abstract: HIV and syphilis screening in pregnancy is universally recommended and is essential to prevent mother-to-child transmission of HIV and syphilis, which can result in lifelong treatment, stillbirth, neonatal death and major malformation. The MENJAGA (Protection) project will be conducted in Indonesia, the fourth most populous country in the world, with numbers of stillbirths among the highest globally; yet screening coverage is among the lowest, with only around 27% of pregnant women tested for HIV and only 2% for syphilis in 2015. Indonesia is targeting elimination by 2030 and is urgently seeking evidence-based, context-specific and low-cost solutions to support the integration of disease-specific elimination efforts within the antenatal care (ANC) service delivery platform, in a way that builds upon existing investments in maternal and child health services. Continuous Quality Improvement (CQI), which involves local ANC teams systematically collecting and reflecting on local data to inform the design and implementation of service delivery, has been effectively used to strengthen ANC services in a number of Sub-Saharan African countries. This approach holds considerable promise for Indonesia, a highly populous and diverse country where a 'one size fits all' approach to the delivery of quality ANC rarely applies. Using a cluster-randomised design, we will evaluate the effectiveness, cost-effectiveness, acceptability, fidelity and reach of a multi-faceted CQI intervention to improve antenatal testing and treatment of HIV/syphilis in ANC clinics in 6 districts across 3 Provinces (West Java, South Sumatra and South Kalimantan). This 3-year multi-disciplinary trial is a partnership between the London School of Hygiene & Tropical Medicine, the Universitas of Gadjah Mada, the University of Sebelas Maret, the Indonesian Ministry of Health and the Kirby Institute.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Strategies to reduce vertical transmission of multi-drug resistant pathogens to neonates (NeoVT-AMR)
Funder: Medical Research Council

Abstract: Neonatal infection is a leading cause of morbidity and mortality in children from in low income countries, and rates of antimicrobial resistance (AMR) in causative organisms are rising rapidly. Strategies to reduce the incidence of neonatal sepsis are urgently required. Early onset neonatal infection (EOS) often results from transmission of pathogenic organisms from labouring mothers to their infants. Application of antiseptic to the genital tract of labouring women and neonates is potentially a cheap, practical, scale-able intervention to reduce transmission of organisms from mother to child and to reduce EOS, however equipoise exists regarding the effectiveness of such an intervention, particularly for resistant organisms. A large-scale clinical trial is required to address this question, but additional data on optimal antiseptic regimes to be tested are required. This pilot study aims to identify the antiseptic strategy to be tested in such a trial. The proposed study will be conducted in a government hospital in Malawi, a very low-income country. It is a randomised controlled trial consisting of two independent strata: labouring women (maternal strata) and unselected neonates (neonatal strata). Each strata will be a 3x2 factorial trial testing the following factors and a control arm: - Antiseptic (3 levels): chlorhexidine (1%), chlorhexidine (2%), octenidine (0.1%) in both strata. Antiseptic will be applied to the skin of neonates and to the perineum and vagina of women. - Frequency (2 levels): single application in both strata plus 4 hourly in maternal strata and 24 hourly in neonatal strata The study outcomes will be change in vaginal and perineal bacterial load in colony forming units (CFU) in the maternal strata and change in skin bacterial load in CFU the neonatal strata. In addition, safety data will be collected on skin and mucous membrane integrity, temperature stability in neonates and on the tolerability and acceptability of the intervention.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: STIs in CHIEDZA
Funder: Medical Research Council

Abstract: Effective sexually transmitted infections (STI) control in adolescents and young people (AYP) is a key priority for low and middle-income countries where HIV and STIs are prevalent. In most low and middle-income countries, symptomatic STIs are treated by syndromic management, yet sensitivity and specificity of this approach for STIs are poor. We propose to evaluate the effectiveness of community-based screening for STIs using newer diagnostic technologies in a Wellcome Trust-funded community-based cluster randomised trial among AYP in Zimbabwe. The aim of the study is to evaluate the effectiveness of community-based screening for and comprehensive management of curable STIs among AYP in reducing the population level prevalence of STIs in a high HIV-prevalence setting. Our objectives are to implement and measure the uptake and yield of STI screening and comprehensive case management offered to AYP aged 16-24 years in community settings in Zimbabwe; assess the impact of community-based STI screening and comprehensive case management on population level STI prevalence among AYP; develop and evaluate a risk assessment tool to predict STI positivity among asymptomatic AYP to inform targeted STI screening; measure the cost-effectiveness of community-based STI screening and comprehensive case management; and to conduct a process evaluation of the intervention's implementation to document its feasibility, mechanisms of action, and the role of local context to identify the key components required for effect, sustainability and scalability. The study findings will help inform policy-makers on how to best integrate newer diagnostics into STI management guidelines for AYP.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Measuring the medium-term impact of school-based interventions as girls transition into adulthood
Funder: Medical Research Council

Abstract: This research will follow-up adolescent girls and young women (AGYW) enrolled in a prior school-based randomised-controlled trial to measure if prior interventions providing a statistically significant effect have a sustained, complementary, or lag effect on sexual and reproductive health (SRH), mental health, and social equity as AGYW transition to adulthood after trial closure. It will examine if gains are lost if outcomes converge to those of AGYW who received no prior interventions. If the trial has a non-significant effect, the follow-up will evaluate if positive lag effects occur. Additional outcomes such as mental health, community perceptions of trial outcomes, continued use and safety of menstrual cups, and COVID-19 impacts will be evaluated. We aim to re-enrol 3,719 participants (90% of original cohort) and conduct two annual biomarker and socio-behavioural surveys over 3 years. Measures will evaluate if prior interventions effect the prevalence of HIV, HSV-2, gender-based violence, age at first marriage, age-equitable partners/husbands, age at first birth, contraceptive use and fertility, stunting of infants, and other maternal health outcomes, mental health and empowerment e.g. employment, partners' educational level, income, and decision-making. Antenatal records will be interrogated to capture maternal and newborn outcomes. Focus group discussions and in-depth interviews will provide contextual data to interpret quantitative findings. Cost-benefits analyses and returns on investment of prior trial interventions on health and social equity will be measured. Building capacity e.g. enhancing mental health research, will be integral to project success. Outcomes will contribute evidence for decision-making on investments to support gender equality for AGYW. Findings, methods, and tools will be widely disseminated to inform the community, researchers, and stakeholders.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Defining upper respiratory colonisation and microbiome evolution in mother-infant pairs following Neisseria lactamica inoculation in late pregnancy
Funder: Medical Research Council

Abstract: Background: Certain infant upper respiratory tract (URT) microbiome profiles (e.g. dominated by commensal Corynebacterium and Dolosigranulum species [spp.]) appear to protect against URT infection. These correlate inversely with potential pathogens (e.g. Haemophilus and Streptococcus spp.), whose presence precedes infection. Pharyngeal colonisation by the harmless infant commensal Neisseria lactamica (Nlac) correlates inversely with N. meningitidis (Nmen) colonisation and invasive disease. Controlled human infection (CHI) with intranasal Nlac reduces Nmen colonisation in adults, and is safe and well-established. Neonatal URT flora arise partly from the maternal URT, although no CHI studies have been done in pregnant or post-partum women or neonates. Many oral and nasal probiotics are safe in pregnancy and breastfeeding, but their effectiveness and impact on neonatal microbiomes is unclear. Objective: To establish whether horizontal Nlac transfer occurs from experimentally-colonised mothers to neonates following intranasal Nlac CHI in pregnancy, and to characterise the impact on the neonatal URT microbiome. Methods: I will assess for neonatal Nlac colonisation by processing URT samples using selective media and targeted PCR. I will study the impact of Nlac CHI on pharyngeal microbiome development in mother-neonate pairs by 16S rRNA sequencing and bioinformatics analysis. If horizontal transfer occurs, I will compare genetic microevolution in paired mother-neonate Nlac isolates. If no horizontal Nlac transfer occurs, I will look for horizontal transmission of other commensals (e.g. Moraxella spp.) by sequencing paired isolates. Opportunities: This study aims to improve understanding of neonatal URT microbiome development, and the impact of CHI in pregnancy. The ultimate aim is to use commensal inoculation to reduce pathogen colonisation and prevent neonatal disease.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Yaba guy che "for the guys": Intervention co-development to increase men's HIV service use
Funder: Medical Research Council

Abstract: In Zambia, the PopART universal HIV testing-and-treatment intervention reached a large number of men, yet younger men aged 20-35 were less likely to be found at home during lay counsellor visits. Community-based hubs established post-PopART reached a high number of men and warrant exploration as a component of a broader strategy to provide HIV services to men. The aim of this study is to co-develop, with men aged 20-35, a multi-component intervention to address system-wide barriers to use of HIV services, including HIV testing and ART. The study will be conducted in an urban community in Lusaka. Participatory qualitative research and crowdsourcing will be used to meet the study objectives. Specifically, we will use community engagement, policy mapping, and participatory workshops to define barriers to HIV testing, and linkage to prevention and treatment services that men perceive as key to limiting their uptake of HIV services. We anticipate that norms will emerge as a key barrier to HIV testing and lack of social support as a barrier to linkage to prevention services and ART. We will adapt existing mobile phone support groups for use with men, to inform acceptability of virtual social support, and will launch an open call to crowdsource ideas on how to address barriers to HIV testing. Ideas will be shortlisted based on applicability, feasibility and likely cost, among other criteria. Subsequently, we will hold a series of workshops to finalise the intervention. The first workshop will refine the crowdsourced ideas, followed by two workshops with men resident in the study community to finalise the design of the broader intervention, including: social support components, location of community-based hubs and a logic model of the anticipated causal pathway of the intervention. Final workshops with regional and national policymakers, among other stakeholders, will refine the logic model and garner support for progression to the main study.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH
Title: Development of a mHealth pathway to expand and enhance comprehensive sexual and reproductive health services for young people in Zambia
Funder: Medical Research Council

Abstract: Adolescents and young people aged 15 to 24 (AYP) in Zambia are disproportionately affected by HIV and STIs and have limited access to convenient, non-judgmental, and confidential sexual and reproductive health (SRH) services including HIV/ STI testing and contraception. Addressing these needs requires services that overcome barriers at individual, social, geographic and system levels. Existing research in sexual health has shown that digital technologies (such as vending machines and mobile phone applications) are acceptable to users and effective at overcoming barriers to service access, by offering increased convenience, privacy and confidentiality. However, there is limited evidence on how these digital technologies can support access to comprehensive SRH in AYP. The aim of this project is to co-produce with AYP a community-based, digitally-supported care pathway that includes: a mobile phone app for receiving sexual health test results; vending machines located in-community dispensing a range of SRH products including: HIV self-testing kits; sampling kits for STIs (Gonorrhea, Chlamydia, Trichomonas, Syphilis, HIV) and contraceptives; and a web application for medical review of test results and treatment prescription. The project will utilise a whole systems, socio-ecological approach to develop a human-centred digital SRH care pathway for AYP. The data collected through focus groups workshops and individual outreach interviews will be analysed using social science expertise in organisational analysis, digital innovation, human-centred, user experience design (UXD) and co-production. Functional prototype versions of the app, vending machine interface, vending machine products, web application and data integration software developed in this project will be ready to be implemented in a future trial.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: INFECTION;REPRODUCTIVE HEALTH AND CHILDBIRTH