London School of Hygiene and Tropical Medicine

UKRI Gateway to Research · FY 2026 · 2026-06

Context and challenge being addressed Low- and middle-income countries have experienced an exponential rise in mortality from cardiovascular disease. Most of these deaths are caused by uncontrolled high blood pressure, or hypertension (blood pressure > 140/90 mm Hg), driven by gaps in implementation of evidence-based treatment. Fixed-dose combination therapies (2-3 blood pressure-lowering medications combined into one pill) offer one potential solution for addressing known barriers to treatment of hypertension. The advantages of fixed-dose combinations over individual pills include improvements in adherence and meeting blood pressure targets, reduced health care costs, and fewer cardiovascular events (e.g. heart attack). Yet, despite strong clinical evidence and promotion in international guidance, fixed-dose combinations for hypertension are not widely or consistently implemented. To date, very little is known about the broader health system factors affecting implementation of fixed-dose combinations for hypertension in low- and middle-income countries. Aims and objectives The overall aim of my Future Leader Fellowship is to improve implementation of fixed-dose combinations in low- and middle-income countries. The first phase of my Fellowship focused on Kenya and The Gambia. I achieved my objectives to identify health system barriers to implementation of fixed-dose combinations and to co-develop, with local stakeholders, a strategy to improve implementation of fixed-dose combinations. In February 2025 I will be piloting and evaluating the feasibility of this strategy in Kilifi, Kenya, and Kiang West, The Gambia. For the renewal phase of my Fellowship, my objectives are: 1. To generate evidence for policy-makers of the economic and health value of the proposed implementation strategy that I am piloting (Work Package 1); and 2. To develop a systematic Plan of Action to promote adoption of the strategy into policy (Work Package 2). For Work Package 1, we will use cost data collected during the feasibility study. We will conduct a Cost-Effectiveness Analysis of the implementation strategy to be compared against a willingness-to-pay threshold and a Budgetary Impact Assessment for national and local governments. We will also go beyond these anlayses to conduct a Value of Implementation Analysis. Value of Implementation is an emerging field that explicitly addresses health system costs incurred to facilitate policy change and effective implementation by comparing the net monetary benefit generated in a Cost-Effectiveness Analysis with the costs of implementation and scale-up. For Work Package 2, I will use methods from Applied Political Analysis. This will include Stakeholder Analysis of a wide range of stakeholders in hypertension treatment policy, using in-depth qualitative interviews and workshops. I will work closely with the Cardiac Societies in both Kenya and The Gambia to develop a Plan of Action to support policy adoption that is informed by the power, positions, and interests of relevant stakeholders. Potential applications and benefits The implementation strategy co-developed in the first phase of my Fellowship could greatly improve hypertension treatment in Kenya and The Gambia. To do so, it must be adopted into policy and scaled-up. The work that I am proposing will generate evidence for policy-makers about the costs and value of investing in this strategy and will develop a concrete, evidence-based plan to promote its adoption into policy. It will also build capacity for health systems research for cardiovascular disease in the UK, Kenya, and The Gambia, and provide an approach to policy-making engagement that can be adapted by cardiovascular disease researchers to other settings.    

UKRI Gateway to Research · FY 2026 · 2026-02

Extreme weather events (‘climate shocks’) are accelerating in frequency and magnitude due to climate change. The 1.3 billion people with disabilities globally are particularly at risk of experiencing negative impacts to their livelihoods and well-being from these events.  For example, they are more likely to live in poverty, have less stable livelihoods, and face social exclusion, making it harder for them to adapt to and resist such shocks. They also tend to be more severely affected by disruptions in health and other critical services. Less documented impacts include reduced access to disability-related supports (e.g., personal assistance, assistive technology) and heightened discrimination. People with disabilities may also have a lower threshold for a ‘shock’, as they may begin to experience negative impacts to their livelihoods, health and social participation from less extreme weather events compared to people without disabilities. Despite their increased risk, people with disabilities are often overlooked in climate responses. Climate-responsive social protection is an important strategy for preventing, mitigating and coping with climate shocks. The Ultra-Poor Graduation (UPG), developed by the NGO BRAC, is an innovative approach to social protection that has been implemented in over 20 countries. It combines short-term cash allowances, provision of productive assets (e.g., livestock), livelihood training, access to credit schemes, and programmes for improving access to health and other services. There is strong evidence that the UPG can reduce poverty and create stronger and more stable livelihoods, including amongst people with disabilities. However, it is not known if these benefits can be maintained in the face of climate shocks. The aim of this fellowship is to investigate how to promote resiliency to climate shocks amongst people with disabilities through disability-inclusive, climate-responsive social protection globally, with a particular focus on Bangladesh – a country considered to be particularly vulnerable to climate shocks. Specific objectives are to: Explore the effects of climate shocks on people with disabilities’ livelihoods, health, and well-being in Bangladesh and globally. Evaluate how social protection mitigates the impacts of climate shocks among people with disabilities, with a focus on the UPG in Bangladesh. Estimate the cost-benefits of UPG among people with disabilities in Bangladesh. Identify adaptations to UPG that could improve resilience to climate shocks, as well as broader learnings on creating disability-inclusive, climate-responsive social protection in diverse settings globally. The findings from this research will provide valuable insights into how climate shocks are affecting people with disabilities, and on how to improve resilience through disability-inclusive, climate-responsive social protection strategies. This evidence will help policymakers, NGOs, and international organisations design and implement more effective social protection programmes and other climate responses that consider the unique needs of people with disabilities. By doing so, the research aims to reduce poverty, improve livelihoods, and promote equity and inclusion for people with disabilities in the face of increasing climate variability. This work will directly benefit the 12 million people with disabilities in Bangladesh and the over 20 countries using the UPG model. It will also contribute to broader global efforts to reduce poverty, strengthen livelihoods, and spur climate action. The research will foster partnerships with key stakeholders in Bangladesh and internationally and build capacity for future research and advocacy, ultimately strengthening global responses to climate shocks.    

UKRI Gateway to Research · FY 2026 · 2026-01

Having more than one long-term medical problem (MLTCs; multiple long-term conditions) can seriously reduce the quality and length of people’s lives. Common MLTC include diabetes, heart disease and lung problems. MLTC are usually more common in older people, but in low- and middle-income countries young people also get MLTCs. This is partly driven by infections such as tuberculosis (TB) which, like MLTCs, are more common in people affected by poverty. TB is an infection caused by a bacteria called Mycobacterium tuberculosis (Mtb) which usually affects the lungs. It is common among working-age adults who have weak immune systems due to other health conditions, such as MLTCs. TB is treated with 6-months of antibiotics. Common MLTCs that increase the risk of developing TB and complicate the TB treatment include: ·       Chronic lung disease (lung damage) from smoking, dust, and other triggers makes it easier for Mtb to cause disease. TB then causes more lung damage. This means that people who are ‘cured’ of TB often have long-term difficulties breathing and working. This can be prevented or improved with exercise and education (called pulmonary rehabilitation) which helps people to live better with chronic lung damage. ·       Diabetes can be due to genetics, lack of nutritious foods, older age, other health conditions, or a mix of these. People with diabetes are more vulnerable to TB, and TB makes diabetes more difficult to control. Without diagnosis and treatment, people with diabetes and TB quickly develop complications such as vision loss, heart and kidney diseases. ·       Mental health conditions are common among people with TB, who are the most vulnerable in society. The side effects of TB treatment and stigma and exclusion due to TB make mental health conditions worse. Overall, TB can be considered a red flag which identifies people at high risk of MLTCs. At the same time, the 6-month period when people with TB are taking daily treatment is an opportunity to treat and prevent MLTCs. This will set people up with better health for their future life. We aim to reduce the impact of MLTCs on the long-term health and wellbeing of people with TB in Zimbabwe. We will achieve this using a combination of education, counselling, peer-support, exercise, nutritional support, and diabetes testing and treatment. Care will be community-based and facilitated by people with lived experience of TB. These services have all been proven to work in other settings but have not been used in this way for people with TB before. We will draw on local experts, including community members, to bring services together and integrate them into the existing TB treatment programme. We will then roll out and evaluate our innovative approach in 13 clinics, comparing the quality of life due to health of people with TB in these clinics to people in 13 clinics where the intervention was not rolled out, as part of a randomised controlled trial. Our aim is to test a program of integrated care that will improve the lives of people recovering from TB.

UKRI Gateway to Research · FY 2026 · 2026-01

Both RTS,S/AS01 and R21/Matrix M vaccines are now prequalified for widespread use by the WHO, marking a significant milestone in advancing malaria control, while the global malaria burden is on the rise again. Although they are still in early stages of rollout in young African children, it becomes crucial to explore how to scale up their large-scale deployment to maximise their effects. However, there is a paucity of knowledge on the R21 vaccine immunogenicity in older age groups. Indeed, such information is currently lacking in schoolchildren/adolescents, and only scarce data are available in adults. R21 is a redesigned version of RTS,S, developed at The Jenner Institute in Oxford. Both include virus-like particles using the Hepatitis B surface antigen (HBsAg) scaffold to display the circumsporozoite protein (CSP), albeit in different proportions. R21 contains only CSP-HBsAg fusion protein (comprising the conserved central Asn-Ala-Asn-Pro (NANP) repeats and the C-terminus of the CSP), with no unfused HBsAg, increasing the CSP antigen density on the particle surface, which results in comparable immunogenicity to RTS,S, even when administered at a five-fold lower dose. An age de-escalation, dose escalation Phase 1b trial in Kenyan adults, young children and infants demonstrated R21 vaccine to be immunogenic across dose and age groups, although anti-NANP IgG antibody titres were inversely related to age, with the highest response to priming vaccination seen in infants. Further studies on R21 efficacy have mainly focused on 5- to 36-month-olds. Vaccine-induced anti-NANP IgG antibody titres have been shown to strongly correlate with vaccine efficacy, with antibody levels in infants about six times higher than in UK adults, although shown to be protective in a human challenge model. A similar age-dependent hierarchy of vaccine-induced antibody responses and associated efficacy was observed between 5- to 17-month-old and 18-to 36-month-old children, though the underlying mechanisms remain largely unknown. A cluster-randomized trial (Seasonal R21 Mass Vaccination for Malaria Elimination, SERVAL) to evaluate the effect of mass vaccination (all ages) with R21/Matrix M on malaria morbidity and community transmission was implemented in The Gambia (low-to-moderate transmission) and Burkina Faso (intense transmission). All eligible residents in intervention villages received three monthly R21 vaccine doses just before the 2024 malaria transmission season, which will be followed by a booster dose vaccination in June/July 2025. Preliminary results show a major impact of the vaccine in The Gambia and across all age groups, while in Burkina Faso, the effect is more modest. This trial offers a unique opportunity to characterise the immune response following R21 vaccination in individuals of different age groups (6-month–3-year-olds (recommended for R21 receipt), 4–14-year-olds, =15-year-olds) living in two areas at the extreme of the transmission spectrum. We propose to measure vaccine-induced immune responses before the first vaccination, 28 days and 12 months after the third vaccination and 28 days, 12- and 24- months following the booster dose and investigate how these responses are influenced by age, malaria transmission intensity, previous cumulative exposure and infection at the time of vaccination. We will also determine whether these responses affect the risk of clinical malaria. This study will generate pioneering data to support the use of the R21 vaccine in older age groups and shed light on the mechanisms underlying differences in vaccine responses that may aid future malaria vaccine development. Furthermore, it will provide invaluable insights to interpret the SERVAL trial results.

UKRI Gateway to Research · FY 2025 · 2025-11

Context Research in economics, social and health sciences, and other areas of empirical study often involves statistical analysis of datasets. These datasets typically contain some missing values, for a variety of reasons. For example, in a cohort study which aims to follow up individuals at a series of visits over many years, some individuals may drop out from the study. Moreover, even when they attend a visit, some individuals may have some variables missing because, for example, they refused to answer a question in a questionnaire. Missing values complicate statistical analyses. They cause the results of an analysis to be less precise than they would have been had there been no missing values. Moreover, analyses of the incomplete data may lead to biased results when those with missing values differ systematically from those with complete data.   The challenge to be addressed There exist a variety of statistical methods that can be used to accommodate missing values in a statistical analysis. One of the most popular is multiple imputation – for a given individual, plausible values for the missing variable (imputations) are generated based on the values of the observed data for that individual. These imputations are typically generated using simple statistical models, which may lead to biased results when these models make incorrect assumptions. In recent years, it has been shown that machine-learning techniques can sometimes outperform traditional statistical models in modelling complex relationships between variables. As such, there has been interest in trying to use machine-learning methods to impute or predict missing values. These approaches however lack theoretical justification, and results may be invalid due to an issue called regularisation bias. The latter occurs because machine-learning methods are optimised for prediction, rather than estimation of parameters of interest.   Aims and objectives The overall aim of the project is to exploit recent fundamental developments in so-called debiased or double machine-learning to develop and implement machine-learning methods that flexibly accommodate missing data. We will do this first for the case where one variable is partially observed, before moving on to the more complex setting where multiple variables have missing values. We will compare the performance of the methods developed with that of existing multiple imputation methods through both simulation studies and application to exemplar datasets. To maximise the impact of our research, we will develop an open-source software package implementing our methods, a user guide with illustrative analyses, and run various dissemination events.   Potential applications and benefits The methods we will develop will be able to be used by researchers faced with analysing incomplete datasets across a range of research fields, including social, health and business research. Unlike the existing imputation methods that are most commonly used, our methods will be less likely to generate biased results, because they flexibly model relationships between variables using machine-learning techniques. Our methods will mean researchers need not concern themselves with the tricky task of deciding how exactly to model the relationships between variables when imputing missing values. Moreover, unlike existing imputation approaches that use machine-learning methods, the approach we will develop will have a strong theoretical underpinning and superior statistical properties.    

UKRI Gateway to Research · FY 2025 · 2025-11

Context It is important to understand the reasons why some people develop particular health conditions and others do not. If we can understand the reasons why people with one health condition may go on to develop other conditions, we can attempt to intervene to prevent this from happening. For example, it is known that people suffering from eczema are more likely than the general population to suffer from heart failure. Some potential reasons for this are increased body mass, or depression caused by coping with eczema, increasing the chance of later heart failure. Causal mediation analysis is a way of investigating the extent to which the impact of a particular condition on a later health outcome is mediated through an intermediate variable which is affected by the exposure and in turn affects the outcome. In the example above that means how much of the effect of eczema on later heart failure is due to depression or weight gain, and how much is for other reasons. Electronic Health Records (EHRs) are the records of medical appointments that are made when you have a health consultation. This project will use anonymised data from a network of GP practices across the UK. For each (anonymous) patient, the data set contains information on all GP visits over a period of several years, allowing us to study the development of health conditions over time (longitudinal measurements). Challenges the project will address Existing analysis methods for mediation with time-to-event outcomes assume longitudinal measurements are made on a regular time grid. Data from Electronic Health Records does not satisfy this condition, since people do not visit GPs at regular intervals. This means that using existing methods to assess mediation in EHRs may give biased results. Additionally, different patients may have different thresholds for visiting their healthcare provide despite having similar symptoms. This is called informativeness of visits, and may lead to a second form of bias if not accounted for in the analysis methods. Aims and Objectives Our project aims to solve these two challenges, by developing new statistical analysis models and software. We will use the Bayesian analysis framework, since this allows all the variables followed over time to be modelled simultaneously, and include full uncertainty on the results. In order to understand in which scenarios the new method are needed, we will carry out a systematic study to quantify the bias caused by using existing analysis methods for EHR data. Synthetic data used for model development and testing will be derived from the real EHR data, ensuring that we are building realistic and useful models. We will make our new analysis methods available through freely available, open-source software, thus enabling researchers to benefit in future analyses. Benefits of the research EHRs provide excellent opportunities for learning about health conditions. They are much more representative of the general population than small studies designed to look at one disease at a time. This research will help improve health through better understanding of disease causing mechanisms, by enabling the utilisation of these huge data sets.    

UKRI Gateway to Research · FY 2025 · 2025-09

Falciparum malaria is the leading parasitic cause of death globally, resulting in 608,000 fatalities in 2022. Cerebral malaria (CM), where the infection affects the brain and causes unrousable coma, is responsible for most malaria deaths and occurs mainly in African children. Malaria is increasing globally following climate change and breakdown in endemic country control efforts, causing malaria transmission to re-emerge or spread to new areas. At least 30% paediatric survivors of CM have neurocognitive deficits, causing significant ongoing functional impairment. The disease is under-studied in adults, where it occurs in different geographical areas with seasonal or irregular malaria transmission, such as India. Well-designed cohorts with serial follow-up assessments are currently lacking in adult CM. Our ongoing research programme in India identified a specific pattern of MRI brain changes in adult CM, and we reported that mild to severe changes also occur in malaria without clinically recognised brain involvement (severe infection without a diagnosis of CM and uncomplicated malaria). The long-term functional consequences of these changes shown for the first time in India are unknown. Our recent UCLH CM case series showed similar MRI findings and demonstrated long-lasting neurocognitive impairment post-discharge. Here, we propose to investigate the occurrence, frequency, and amplitude of focal and global brain changes in adult patients with falciparum malaria admitted at two joint hospitals in Rourkela, India, and assess their evolution over time using high-resolution MRI (3 Tesla). We will combine this approach with stringent serial and targeted psychometric tests to reveal associations between specific brain changes and neurocognitive deficits. In parallel, we will evaluate the predictive value of retinopathies, EEG, and relevant biomarkers candidates on admission to identify individuals at risk of developing neurocognitive sequelae. We anticipate that the results generated by our project will fill critical knowledge gaps on the effects of falciparum malaria in adults and inform the design of new tools for their diagnostic and prognostication, ultimately supporting management and targeted neurorehabilitation efforts globally.

UKRI Gateway to Research · FY 2025 · 2025-09

Stillbirths remain a significant yet under-prioritised public health issue in Nigeria, which impacts women and their families. In 2021, 182,000 babies in Nigeria died after 28 weeks of pregnancy, either before labour began or during childbirth. These are known as stillbirths, and they accounted for nearly 10 percent of all stillbirths worldwide that year. Imo State, in southeast Nigeria, presents a striking paradox. Although it has the highest access to maternal health services in the region, it also records one of the highest rates of stillbirths. My DPhil research, the first case-control study on this issue in Imo State, found that women who were referred between hospitals had nearly four times the risk of experiencing a stillbirth. This suggests that delays in reaching appropriate care, especially during labour, may be a major contributing factor. Building on this research, I now plan to study how travel time to health facilities affects the chances of stillbirth compared with livebirths. One critical gap in understanding stillbirths is what happens between the time a woman decides to seek care and when she actually arrives at a hospital. These are known as “Type II delays” and are particularly important in fast-growing urban areas like Imo State. A ground-breaking study in Lagos, Nigeria, by my proposed mentor, Associate Professor Banke-Thomas, showed that longer travel times significantly increased the risk of stillbirth among women who arrived in emergency situations. His research used data from 3,378 births, including 408 stillbirths. To carry out similar research, I will need advanced training in spatial epidemiology, which studies how geography and health outcomes are linked. I plan to take specialist courses at the London School of Hygiene and Tropical Medicine, where I will also have the chance to learn from experts like Chris Grundy, a leading human geographer. These courses will equip me to analyse travel time data using two key sources. One is my existing dataset from my PhD, which includes 432 stillbirths and 381 livebirths. The second is an innovative dataset developed by my mentor using Google data to calculate more realistic estimates of how long it takes to reach care. I also bring relevant experience from my time as a research fellow on the OnTIME project, which studied access to emergency obstetric care across Nigeria, including Imo State. Although that project found that 97.3 percent of women in Imo live within 30 minutes of a hospital, a travel time of more than 10 minutes was linked to a higher risk of stillbirth in the Lagos study. This link has not yet been explored in Imo State, and my project aims to address this gap. By combining advanced spatial tools with real-world data, this research will provide vital insights into how travel time affects stillbirths. I will also examine whether babies who die before labour starts (antepartum stillbirths) are affected differently than those who die during labour (intrapartum stillbirths). This distinction will help highlight critical gaps in access and responsiveness of emergency obstetric care and inform targeted solutions in Imo State. The one-year fellowship will provide a strong foundation for my future career. I plan to publish my findings in a peer-reviewed journal and share them at public health forums. Ultimately, this study will help reduce preventable stillbirths by ensuring women can reach life-saving care in time.

UKRI Gateway to Research · FY 2025 · 2025-08

Your gut houses a bustling community of trillions of microbes, mostly bacteria, containing more genes than the human genome. These microbes are involved in functions crucial to your health. These bacteria help to digest the food you eat, and they help with absorbing and synthesizing nutrients too. Gut microbes are involved in many other important processes including your body weight, your defense against infections, as well as your brain functions and they may even alleviate your anxiety. Not surprisingly, there is intensive research to find ways to improve our health by controlling and manipulating the resident microbes of the gut. Unfortunately, recent research has shown that our gut may also house other microbes, hidden, that cause infections when disseminate from the gut to other tissues. In fact, a number of studies interrogating patients admitted to the hospital that later develop infections in the blood have clearly established that the patients were the carriers in their guts in an asymptomatic way of the microbe causing the infection. Klebsiella pneumoniae is one of these microbes with the ability to co-exist peacefully in our gut but with also the ability to become a deadly microbe if reaching our tissues such as the lung or the blood. Klebsiella has been singled out as an urgent threat to human health by the UK Government, the U.S. Centers for Disease Control and Prevention, and the World Health Organization due to extremely antibiotic resistant strains. The increasing isolation of strains resistant to "last resort" antibiotics has significantly narrowed, or in some settings completely removed, the therapeutic options. This is particularly alarming in low and middle countries. This research is designed to unveil the incognito lifestyle of Klebsiella in our gut and to establish how Klebsiella can cross the gut to reach other tissues. We will characterize the gut environment promoting Klebsiella colonization and which one is hostile. Particularly, we will identify which of the microbes of our gut are able to out-compete Klebsiella and which ones favour Klebsiella colonization. Lastly, we will define which of the small genetic variations that difference each of us render our gut permissive for Klebsiella colonization, and which ones are restrictive. The findings of this research shall be the foundation of innovative therapeutics to prevent the gut colonization of Klebsiella. These new therapies may involve boosting our gut defenses to generate a harsh environment for Klebsiella, the use of rational design probiotics that include gut microbes efficient eliminating Klebsiella, and antibodies-based treatments or vaccines targeting Klebsiella.

UKRI Gateway to Research · FY 2025 · 2025-06

Current malaria prevention tools offer only partial protection against malaria, hence co-implementation of malaria prevention strategies are preferred. Combining tools allows different points in the malaria transmission cycle to be targeted and/ or improve community protection against malaria as individuals may opt for one tool that is more acceptable to them in preference to having no protection. The impacts of different mixes of interventions on individual level and community protection against malaria in routine settings are poorly understood but essential information to support country level strategic planning with limited resources. In this proposal we aim to evaluate the effectiveness of co-implementation of national strategies of malaria vaccines (MVac), piperonyl butoxide and pyrethroid-treated long-lasting insecticidal nets (PBO-LLINs), and malaria chemoprevention (Perennial Malarial Chemoprevention - PMC and Seaonal Malaria Chemoprevention - SMC) on malaria incidence, and to identify sustainable and integrated supplementary delivery models that optimise acceptability and feasibility to these strategies. The OPTiMIX study team, a collaboration between the Fobang Institute of Innovation in Science and Technology (FINISTECH) Yaounde, Cameroon, The Institut Nacional de Sante Publique (INSP), Abidjan, Côte d'Ivoire and the London School of Hygiene and Tropical Medicine (LSHTM), London, UK have been working together since 2023 to monitor the roll-out of PMC in moderate-high malaria transmission study sites in Cameroon and Côte d'Ivoire. Each study site consists of a control district where the study population receives standard-of-care malaria prevention, and an intervention district where the population receives the new PMC intervention.  The impact of PMC implementation is evaluated using active and passive cohorts to measure incidence of malaria and anaemia, intervention acceptability, feasibility and cost-effectiveness. In 2024, our PMC intervention sites started (or will start) to receive MVacs (RTS,S in Cameroon in March, and R21 in Côte d'Ivoire  in October). In 2025 all study districts will receive PBO-LLINs, and in 2025 our control study district in Côte d'Ivoire will receive SMC. The routine co-implementation of this mix of interventions provides an exciting opportunity to optimise and measure the impacts of combinations of malaria interventions including MVacs. The OPTiMIX study will do this through the following three objectives: Objective 1: Measure the effectiveness, coverage, and safety of national co-implementation of combinations of MVac, PBO-LLINs and chemoprevention (PMC and SMC) at reducing the burden of malaria. This will be achieved through leveraging four large established infant and child cohorts at high risk of malaria. We will extend active and passive cohorts for 3 years to capture the individual and community impacts of various combinations of interventions. The main analysis will use Cox regression on the outcome of clinical malaria. Objective 2: Identify sustainable and integrated supplementary delivery models to support improved co-implementation of MVac, PBO-LLINs and chemoprevention. This will be achieved by applying a process improvement intervention (the LEAD framework) that supports key stakeholders at different levels of the delivery continuum in co-production and feedback cycles to create sustainable and integrated supplementary delivery models. We will assess supplementary delivery methods and interventions mixes through measures of acceptability and implementation feasibility. Objective 3: Develop and test a transferable process for assessing and optimising co-implementation of preventive malaria control interventions and elucidating the programme theories underpinning the process. Throughout the study we will build and test programme theories, ultimately deriving final programme theories underpinning MVac, PBO-LLINs and chemoprevention (PMC & SMC) co-implementation.  

UKRI Gateway to Research · FY 2025 · 2025-05

This proposal links two epidemiological studies and one vaccine effectiveness study aimed at addressing the public health challenge of Mpox in Sierra Leone. The outbreak is ongoing and there is an urgent need to collect these data as soon as possible. The MOVIE-SALONE study focuses on understanding the kinetics of viral elimination, shedding light on how MPXV interacts with host tissues and immune defences, and informing endpoint selection in therapeutic trials. The TRACE-SALONE study aims to determine the Secondary Attack Rate (SAR) in MPXV outbreak settings, assessing host susceptibility within specific populations, offering vital data to target interventions towards vulnerable groups and informing vaccine efforts by contributing to the assessment of vaccine effectiveness endpoints. The third study, VE-SALONE, examines vaccine effectiveness for a single dose of the MVA-BN (JynneosTM) vaccine against MPXV infection and Mpox disease.

UKRI Gateway to Research · FY 2025 · 2025-04

In adolescence, health-related behaviours are adopted that will have substantial positive or negative impacts on the individual's short- and long-term health, educational attainment, and employment prospects. However, in most low-income countries few adolescents have any contact with health services, especially for health promotion and disease prevention, and services are not always appropriate for their needs. Due to resource constraints there is often limited capacity to provide high-quality youth-friendly health services. Technological advances provide opportunities to deliver services and information away from traditional clinical settings, hence reducing barriers such as cost or confidentiality. Adolescents may be particularly receptive to digital platforms that allow them to self-manage their health and well-being. What is Y-Check? The programme screens and treats/refers adolescents for common conditions through health check-ups in younger (10-14y) and older (15-19y) adolescents. Adolescents are only screened for conditions with an accurate and acceptable test and a locally accessible effective intervention e.g. mental health, HIV, vision and hearing, anaemia. What exactly has been done so far? We developed, pilot-tested, implemented and evaluated the innovative Y-Check programme and an accompanying digital platform in Zimbabwe. Check-up visits took place at schools for younger and older adolescents, and in the community for older adolescents. The youth-friendly digital platform reduced the workload of staff by allowing adolescents to self-screen using questionnaires (e.g. mental health, risk behaviours) and pre-existing apps (to test hearing, eyesight). What were the main outcomes? Answers to the following questions - Do adolescents attend the screening and referral appointments? What impact do visits have on their health and education? How much does it cost for an adolescent to be screened and to obtain the recommended care for a condition? Is this a good value for money? What is innovative about this study? The approach is innovative and novel, because, few LMICs currently provide check-up visits for adolescents and in countries where they are provided, the visits don't always meet the needs of adolescents e.g. don't include mental health screening. This proposal takes the innovative and bold step of moving from condition-specific health programming towards an adolescent-centered approach focusing on what matters most to adolescents. This is the first empirical study to have investigated the effectiveness and cost-effectiveness of multi-component adolescent health check-ups. Specific innovations: - Youth Researchers participated in a human-centered design approach to intervention development - Digital platform on which adolescents completed some of the health screening activities, saving consultation time and improving the quality and efficiency of data collection - Novel adolescent engagement activities including crowdsourcing contests Why Zimbabwe? Zimbabwe is an ideal location for Y-Check with great potential for scale-up given the close collaboration between the Biomedical Research and Training Institute and the Ministries of Health and Education, the emphasis on prevention within the 2018 School Health Policy, and the absence of other good ways to screen and refer adolescents. In other African settings, there is considerable interest in adolescent check-ups and the model has recently been adapted and implemented in Tanzania and Ghana. In this next phase, we propose to conduct additional data analysis and mathematical modelling to decide on the best content and format for a Phase 2 Y-Check intervention, to design a rigorous evaluation study to determine the Phase 2 interventions' effectiveness, and to estimate the potential longer-term impact of prevention interventions in adolescence.

UKRI Gateway to Research · FY 2025 · 2025-04

Malaria, an infection caused by Plasmodium parasites transmitted through infective mosquito bites can cause severe illness and remains a significant global health concern. In Southeast Asia, while progress has been made against major human malaria parasites, simian malaria parasites, including Plasmodium knowlesi, have emerged as a major source of zoonotic infections. In Malaysia, P. knowlesi now accounts for all malaria cases and together with recent outbreaks also reported in Thailand this parasite presents a major challenge to malaria elimination in the region. P.knowlesi is not affected by standard malaria control approaches and Malaysia, which has made exceptional progress in reducing P.vivax and P.falciparum is unable to be certified malaria free by WHO because it has P.knowlesi cases. Currently WHO guidlines are that P.knowlesi should be at  ‘negligible’ risk, which will require a significant reduction in the number of zoonotic malaria cases in Malaysia. This proposal aims to facilitate that reduction.   Our previous work has identified areas of rapid land use and land cover change as areas associated with both the primate host and mosquito vectors host of P.knowlesi. Thus individuals who work in these areas such as loggers and plantation workers are at highest risk of infection and developing disease. Our work will comprise of 3 aims. Firstly, we will work with partners to refine the P.knowlesi risk maps to identify using contemporary environmental and case report data.  We will focus on the identification of specific sites for this study but the approach will provide a national and regional resource for future surveillance and control activities. Secondly, using the sites in aim 1 we will identify high risk populations withon these areas and  evaluate control methods to reduce the incidence of infection in these people. The primary  intervention for which the study will be be powered is a cross-over chemoprophlatic study monthly using Dihydroartemisinin piperaquine in individuals. Infection will be assessed by a novel Loop-mediated isothermal amplification (LAMP)  which has emerged as a promising tool for molecular malaria diagnosis due to its simplicity and rapidity. Our preliminary studies suggest LAMP's effectiveness in diagnosing simian malaria species. We will also evaluate the accpetability and utility of personalised  vector control namely insect repellent (DEET)-impregnated anklets and wristbands. These have shown promise in reducing mosquito bites, however, their effectiveness against zoonotic malaria vectors remains unexplored and we therefore aim to evaluate this personal-level protection in high risk workers. Thirdly, we will work with local and national stakeholders (local small scale farming communities, plantation owners, MoH) to understand if and how the approaches can be adopted and used more widely. We will examine different potential delivery and funding scenarios to advise regional and national control programmes on optimal methods to reduce P.knowlesi in these high risk groups. Together these aims will reduce the burden of P.knowlesi at individual and community levels in Malaysia and allow wider adoption in affected areas.

UKRI Gateway to Research · FY 2025 · 2025-04

The Philippines has set a visionary goal of attaining zero or significantly reduced infections with malaria, several vaccine-preventable (VPDs), and neglected tropical diseases (NTDs) through an effective healthcare system by 2030. Yet, the country faces challenges in realising this goal. Malaria elimination initiatives are threatened by sub-patent infections that are missed by conventional diagnostics and sustain transmission, antimalarial drug resistance prevalent in Southeast Asia, increasing worldwide vector resistance to insecticides, and diagnostic failure. After years of consistent progress in defeating malaria, with only the province of Palawan reporting cases, the Philippines is currently experiencing a resurgence of Plasmodium falciparum and P. vivax. Consequently, many VPDs and NTDs persist, and in some cases result in outbreaks or re-emergence, despite effective measures. Although the Philippines has relatively low burdens of these diseases, achieving the ambitious goal of elimination necessitates building and, equally importantly, maintaining robust monitoring and surveillance systems for co-endemic diseases. Additionally, training a cadre of scientists who embrace innovations in laboratory, epidemiological, and data sciences is essential to support the country's determination to create a future free from the burden of many of these diseases. Our project, CoSTaR, rises to the challenge of disease elimination by developing sustainable and scalable solutions for malaria and priority infectious diseases in the Philippines. We will employ and refine effective molecular and serological platforms to measure residual malaria transmission in the population (WP1/2). Our serological platform for malaria is flexible and adaptable, permitting the simultaneous assessment of exposure to VPDs and NTDs that may persist in a population. We will develop this platform to address the country’s need for a first-of-its-kind integrated multi-disease monitoring system (WP5). Representing a paradigm shift in elimination efforts, this platform offers an evidence-based solution to understand population immunity against these diseases, define disease-specific transmission dynamics, and identify demographic and spatial risk factors associated with pathogen exposure, thereby complementing the government’s elimination initiatives. Solutions are also warranted to determine the biological factors that may affect residual malaria transmission. Thus, we will define the genetic structure and antimalarial drug resistance profiles in persisting parasites (WP3). Additionally, we will analyse the human host response enabling parasite persistence (WP4). In a supplementary study, we will provide baseline data on markers of vector resistance to insecticides currently being used in the country (SS). Our innovative solutions leverage the equitable and enduring partnership between the Department of Health’s (DOH) Research Institute of Tropical Medicine (RITM) and London School of Tropical Medicine and Hygiene (LSHTM) – lead teams in this project. Capacity strengthening and knowledge exchange, complemented by community engagement and stakeholder outreach, constitute the cornerstone of our project strategy (Cores). Along with Palawan State University (PSU), we will empower researchers and communities to be actively involvement in disease awareness initiatives. We will further enhance capacity in laboratory investigations and applied epidemiological analysis, nurture leadership and collaborative efforts among our researchers, and optimise the impact of our initiatives through close engagement with the local Municipal Health Office (MHO), and a wide range of local, regional, and national stakeholders. Ultimately, our efforts aim to strengthen the resilience and sustainability of disease monitoring in the Philippines, improve health outcomes, and leave a legacy of innovative and impactful research, along with well-trained researchers who will advance global health practices.

UKRI Gateway to Research · FY 2025 · 2025-03

PROBLEM: African newborns face the highest risk of death - on average about 14-times more likely to die than a UK-born baby. The Sustainable Development Goals (SDGs) include a specific target for neonatal survival, catalysed by our team, that every country should have a neonatal mortality rate (NMR) of less than 12 deaths per 1000 live births by 2030. However, almost all 46 Sub-Saharan African countries are currently off-track. Across the African continent most women now give birth in facilities, yet 1.1 million African newborns die every year because cost-effective, lifesaving neonatal care is not provided. PARTNERSHIP: Partnership for Accelerating Neonatal Survival Across Africa (PANSAA) brings together two African-led platforms: (1) Newborn Essential Solutions and Technologies (NEST360) and (2) The African Neonatal Association (ANA). This partnership would deliver the largest network for newborn care on the continent. NEST360 and ANA recently signed a formal Memorandum of Understanding (MoU), but we cannot reach our potential for impact without funding like this UKRI partnership grant, providing high-return on investment at low-risk, given funding for the two underlying networks. NEST360 Alliance works with five African governments and an international consortium of 22 organisations (17 in Africa), to implement evidence-based small and sick newborn care with multi-level health system change through innovative devices, education ecosystems, and locally-owned data and dashboards. ANA includes neonatologists, and paediatricians from nearly all 46 Sub-Saharan African countries, to focus on elevating and improving clinical neonatal care. PEOPLE AND AIM: Our team is over two-thirds women, and majority African, bringing inter-disciplinary technical expertise in clinical care, data science, implementation research, policy, as well as parent representation to achieve our collective aims accelerating newborn health, and also African leadership. Our partnership elevates the voices of African parents in co-designing and helping to answer applied research questions. PROPOSED APPROACH: PANSAA involves five workstreams (WS). In WS1 we would pool large datasets from NEST360 (137 neonatal units) and ANA (23 units), enabling comparable data for >150,000 newborns per year in eight countries collectively accounting for over 60% of Africa’s neonatal deaths. We will use these data to identify priority applied research questions, co-created with parents, clinicians, biomedical engineers, laboratory personnel, and linked to government and United Nations partners. We will focus initially on implementation research for two high-impact topics: Kangaroo Mother Care (KMC-WS2) and neonatal infections (WS3). Research findings emerging from these two research incubators will be published and disseminated for uptake and policy action. Together we will translate data into actionable changes in quality of care and lives saved. As well as transforming the health of the next generation of newborns, we will grow the next generation of African implementation researchers (WS4). Early career researcher development opportunities will include remote training, annual skills-building workshops, as well as mentorship in order to undertake research, publish results, and develop grant applications for partnership sustainability. Findings and tools will be shared widely though NEST360 and UNICEF’s ?www.NewbornToolkit.org, which had more than 28,000 users from 170 countries during 2023  enabling uptake of findings globally (WS5). We are committed to including French-language speakers through translation of key tools and learnings, bilingual webinars, and engagement opportunities. Together we can give African newborns an equal opportunity to survive and thrive, also helping to close gaps in equity for neonatal research leadership including by race, gender and language.

UKRI Gateway to Research · FY 2025 · 2025-03

Climate variability and change is adversely impacting the burden of food- and water-borne illnesses including diarrheal diseases. Despite overall decrease in global prevalence, diarrheal disease remains a leading cause of morbidity and mortality in low- and middle-income countries (LMICs). Currently, LMIC countries lack a coordinated assessment of the climate change related diarrheal disease burden, and there is a pressing need to enhance community resilience against this threat given ongoing climate change. With the support from Belmont Forum’s first round of Climate, Environment and Health (CEH-I) funding, we established a multinational consortium (AWARD-APR) to conduct a regional assessment of climate change related diarrheal disease burden in the Asia Pacific Region (APR). To date, our multinational team has successfully: 1) compiled diarrheal disease databases for Nepal, Vietnam, Taiwan, and Indonesia; 2) developed uniform extreme weather event (EWE) exposure metrics; 3) generated scientific evidence regarding how climate change related EWEs have exacerbated the burden of diarrheal disease in APR; and 4) built a prototype early warning system (EWS) for Nepal, Taiwan, and Vietnam using classical statistical methods. We have learned that accuracy of the prototype EWS improves considerably when most recent surveillance disease data with finer temporal resolution is available, as was the case in Taiwan. Unfortunately, such data is not available in most LMIC settings that bear the disproportionate burden of diarrheal disease. In AWareness Against Health ThReats of Climate ChangE (AWARE), we will collectively work to enhance community resilience to climate change related increases in the burden of diarrheal disease through integrated research, community engagement, and partnerships. We will build on and expand our partnership to include South Africa and the UK as well as further develop our analyses to quantify the impact of climate change on waterborne disease to inform national adaptation planning. To address limitations related to availability of health data, we will utilize unique datasets consisting of over-the-counter (OTC) medication (loperamide) sales data along with diarrheal disease hospitalization records collected by our South African partners, to explore if such OTC medication data can be used as a novel proxy for underlying disease dynamic in a community. We will also expand our early warning prototype by incorporating modern machine learning (ML) to improve our predictive capacity in high-risk countries (India, Indonesia, Nepal, South Africa, Taiwan, Vietnam). We will carry out a prospective evaluation of our EWS to predict disease burden ahead of time. We will also conduct evaluation studies to assess the benefit of the climate information delivered through mobile app. To ensure that the EWS is effective and feasible, we will work with local communities, non-governmental organizations (NGOs), and local health departments on how to use this mobile app tool to enhance community resilience against health threats of climate change. In Nepal, we will work with female community health volunteers (FCHVs) and staff nurses at Dhulikhel Hospital's 18 rural health centers on the use of the EWS mobile app to prepare for potential diarrheal disease surges in their communities. Our academic partners in other countries will carry out similar activities in partnership with local NGOs (Alliance for Collaboration on Climate & Earth Systems (ACCESS) in South Africa; Gugah Nurani Indonesia (GNI); International Climate Development Institute (ICDI) in Taiwan, and Aarogyam Knowledge to Action Society (AKAS) in India). Since climate change-driven EWEs are projected to continue increasing in the foreseeable future despite mitigation efforts, there is a pressing need to enhance public health adaption measures including preparedness, capability for rapid mobilization of public health resources, healthcare infrastructure resilience, and awareness training. We contend that now is the time to develop, implement, and evaluate climate/weather-informed EWSs to enhance community resilience against the health threats of climate change. Leveraging novel datasets and recent advances in ML, we will enhance the predictive power and geographic resolution of our prototype EWS to forecast diarrheal disease burden at seasonal to sub-seasonal (S2S) scales. AWARE is guided by its’ central theme of leveraging artificial intelligence to synthesize high dimensional data and develop EWSs in partnership with local stakeholders to enhance resilience against health threats posed by climate change. We will achieve our objectives through execution of following four work packages (WPs): Work Package 1: Quantify the impact of climatic factors, including phases of ENSO, monsoon anomaly, and extreme events (extreme heat, extreme precipitation, flooding) on diarrheal disease transmission and identify modifiers of risk, such as sociodemographic and geographic factors. Hypothesis 1: Diarrheal disease incidence will be associated with these climatic factors, and the associations will vary by sociodemographic factors, access to water and sanitation, elevation and latitude. Work Package 2: Measure the extent to which over-the-counter (OTC) medication data can be used as a novel proxy for the most recent diarrheal disease incidence. Hypothesis 2: OTC medication data will predict underlying pediatric diarrheal disease incidence in South Africa. Work Package 3: Incorporate modern machine learning (ML) based methods to enhance predictive capability of our classical statistics-based prototype EWS, and carry out a prospective evaluation of our EWS to predict disease burden weeks to months ahead of time. Hypothesis 3: Deep state space models for time-series forecasting enables S2S forecasting for diarrheal disease. Work Package 4: Co-develop a diarrheal disease EWS mobile app with community partners to provide alerts and advice, and thereby enhance resilience against health threats posed by ongoing climate change. Successful completion of our work will lay a foundation for climate resilient society where communities will be able to anticipate these threats ahead of time, prepare for them, and respond to them when it is time, rather than simply reacting to them after the fact. In doing so, this proposal addresses the recent United Nations’ initiative, Early Warnings for All. With the multi-national group of stakeholders involved as equal partners throughout our work, we will be able to successfully translate our research into actionable climate and health knowledge within our partner communities.

UKRI Gateway to Research · FY 2025 · 2025-03

Around 11 million people developed tuberculosis (TB) in 2021, and 1.6 million died from the disease. Current control strategies are insufficient, with global TB incidence falling by only 2% per year. One reason for the slow decline may be widespread reliance on passive case detection - requiring people with TB to present to healthcare services with symptoms. This means that people can be infectious for months or years before diagnosis, and an estimated 40% of incident TB was not diagnosed in 2021. Active case finding (ACF) - the systematic screening of high-risk groups or populations - is one way to find people with TB earlier, leading to reductions in transmission. The World Health Organization recommends ACF in areas with a high prevalence of TB. Recent National Strategic Plans from countries as diverse as South Africa, Uganda, and India contain plans to scale-up ACF in high risk populations. Despite the scaling up of ACF activities, considerable uncertainty remains as to their likely impact, and how it varies between approaches and settings. Three randomised control trials (RCTs) estimating the impact of ACF on transmission have been conducted. One trial achieved an impressive 50% (95% CI 22-68%) reduction in the prevalence of infection in children (a proxy for transmission), demonstrating that community ACF can be a highly effective in reducing transmission. The other trials used less intensive intervention approaches, and found no evidence for reductions in transmission. A fourth RCT found a reduction in TB prevalence, but did not estimate reductions in transmission. Mathematical modelling suggests that the differences between the trial results cannot be explained by differences in the tests used or numbers of cases detected. There is a need to understand factors that affect the reductions in TB incidence achieved through ACF, and to identify less intensive and expensive ACF approaches that can lead to reductions in transmission. Mathematical modelling can be used to predict the impact of ACF on TB incidence. However, assumptions typically made in models may not be correct, and models of ACF have rarely been validated using empirical data. In particular, we have identified three factors that may alter the impact of ACF on TB incidence: A) People who have been screened in previous rounds may be more or less likely to seek or accept screening. B) Coverage tends to be lower in men than in women, despite higher TB prevalences in men. C) The probability of participating in ACF may be higher for people who were closer to seeking care and receiving a diagnosis passively. The impact of these factors may vary by intervention design and setting.

UKRI Gateway to Research · FY 2025 · 2025-03

Campylobacter is the leading cause of foodborne diseases annually in the UK, costing the country's economy a significant amount of money each year. Specifically, the Food Standards Agency estimates that Campylobacter infections alone incur a hefty £900 million expense, out of a total of £1.5 billion for all foodborne infections. Particularly, Campylobacter jejuni species is responsible for over 80% of these cases. This bacterium is becoming increasingly resistant to commonly used antibiotics. Remarkably, it naturally resides in birds, where trillions of these bacteria coexist in their guts without causing harm. However, just 100 of these bacteria can lead to severe illness in humans. Consuming or handling poultry is the main way humans contract the infection, which can result in symptoms like bloody diarrhoea, fever, and abdominal pain. In areas with limited resources, Campylobacter infections are particularly prevalent among young children, leading to health issues such as stunted growth, lifelong physical and cognitive impairments, and in severe cases, death. Despite its prevalence and importance, our understanding of how C. jejuni causes disease is limited when compared to other gut pathogens such as Salmonella. Recently, we have identified many strains of C. jejuni that have a Type VI Secretion System (T6SS). The T6SS acts as a weapon firing bullets (toxins known as effector proteins) that neutralise bacterial competitors, thereby conferring them a competitive edge within a host environment. The functions of C. jejuni T6SS effectors, particularly in chicken and human host environments and their impact on the resulting infection outcome remains unclear. Our research suggests that T6SS and its effectors equip C. jejuni with antibacterial properties to thrive in specific host environments. By analysing the genomes of C. jejuni, we have identified a new range of these effectors and we hypothesise that these are important mediators of C. jejuni pathogenesis and niche establishment. To test this, we propose a multidisciplinary research programme. Our aims and objectives include (1) characterisation of how the T6SS and its effectors of C. jejuni contribute to antibacterial competitive fitness; (2) to determine how different human and chicken in vitro host gut models impact the functionality of the T6SS; and (3) characterise how C. jejuni T6SS and its effectors impact the chicken gut microbial population structure in an in vivo colonisation model. These insights hold transformative potential, informing the development of new antimicrobials based on T6SS toxin mechanisms and novel vaccine targets derived from characterised effectors. The increasing prevalence of Campylobacter infections, coupled with the growing challenge of antimicrobial resistance, presents a significant strain on public health resources, demanding urgent action. To address this pressing issue, our cutting-edge, interdisciplinary project aims to unravel the complex molecular and cellular mechanisms underlying C. jejuni T6SS and effector functions in different hosts, directly aligning with a key BBSRC objective, understanding the rules of life. The knowledge accrued by our research will improve our understanding of this important human pathogen and how it causes disease, with the goal of developing evidence-based interventions to prevent and treat infections and thus improve health. Our impact aligns closely with key pillars of the BBSRC; sustainable agriculture and food, integrated understanding of health and tackling infections.

UKRI Gateway to Research · FY 2025 · 2025-03

With an estimated 1.25 million annual cases and 214,000 deaths, childhood tuberculosis (TB) remains a serious threat to global child health. More than 70% of the global childhood TB estimates occur in the World Health Organisation (WHO) Africa and southeast Asia region where childhood cases remain underreported due to difficulties with diagnosis. Currently, the gold standard for diagnosis of pulmonary TB involves culture of Mycobacterium tuberculosis (M.tb), the causative organism for TB disease, in sputum or other respiratory samples. However, sputum samples are difficult to obtain in children, particularly in young children. Even when sputum or other respiratory samples are successfully obtained, microbiological tests for TB such as M.tb culture or GeneXpert Ultra are less likely to have positive results in children; this is because children are more likely to have TB caused by a smaller number of M.tb. Therefore, diagnosis of childhood TB is often made without laboratory confirmation and instead based on combination of non-specific clinical and radiological features, with high likelihood of missed or clinically-significant delay in diagnosis. Hence, TB is becoming increasingly responsible for childhood morbidity and mortality caused by a treatable infectious disease. The WHO has identified the development and validation of non-sputum biomarker-based tests for detecting TB in children as a major research priority. Such tests should enable fast and accurate distinction between TB and other respiratory diseases (ORD) and perform in all children equally. Our research to date has reported the discovery of a novel 3-marker host protein biosignature of childhood TB (IL-1ra, IL-7 and IP-10) from utilising blood samples collected from HIV-uninfected children in The Gambia. The biosignature was identified in supernatants generated from small blood samples after overnight incubation and without antigenic stimulation. This biosignature reliably distinguished children with TB disease, including those missed by microbiological tests, from those with ORD, with its performance independent of age and nutritional status of the children. We are now applying for funds to validate our 3-marker host protein biosignature in the laboratory, and to refine the biosignature and optimise its performance further, using a unique combination of bio-banked and well-characterised samples obtained from independent paediatric cohorts recruited in Mali, Nigeria, Tanzania and The Gambia. Our specific objectives are to: Estimate the ability of the 3-marker biosignature to classify TB disease from ORD in HIV-infected and HIV-uninfected children from Mali, Nigeria, Tanzania and The Gambia. Compare the predictive accuracy of the 3-marker biosignature between unstimulated QuantiFERON supernatants and serum samples of children from Mali, Nigeria, Tanzania and The Gambia. Estimate the ability of the specific gene expression of the 3-marker protein biosignature (i.e. the biosignature-specific mRNA expression) to classify TB disease from ORD in HIV-infected and HIV-uninfected children from Mali, Nigeria, Tanzania and The Gambia. Determine the added value of combining the biosignature-specific mRNA expression with the protein biosignature to distinguish TB disease from ORD in HIV-infected and HIV-uninfected children from Mali, Nigeria, Tanzania and The Gambia. Our research team members have expertise in paediatrics, childhood TB and biomarker discovery. This proposal provides a unique platform to validate our promising biosignature and demonstrate the utility of serum as a non-sputum sample for biomarker-based diagnosis of childhood TB. Following the research project, it will be possible to develop the protein biosignature into a biomarker-based immunoassay test that uses, for example, micro-ELISA platforms based on microfluidic technology.

UKRI Gateway to Research · FY 2025 · 2025-02

COPE will develop advanced Early Warning and Decision-support Systems (EWDS) for heat and air pollution exposure in two major urban conglomerates in India – Delhi and Kolkata. The research is co-designed and will be conducted in collaboration with user groups, including from vulnerable communities, and stakeholder partners from health care sector and other governance actors. Outcomes of the research will be operationalized through partnerships with governmental agencies. COPE will identify health risk hotspots beyond the select cities and provide risk projections under different climate scenarios with a goal to establish guidance for EWDS in other high-risk areas. COPE aims to investigate and fill critical knowledge gaps concerning: 1) The health risks associated with co-exposure to elevated levels of heat and air pollution in the Indian context. 2) Optimal structuring of EWDS for timely early warnings for heat and air pollution to derive maximal health benefits, emphasizing the needs of most at risk socio-demographic groups and accounting for interactive affects arising from co-exposure to heat and air pollution. 3) Socio-cultural, behavioural, and economic factors that may hinder the adherence to EWDS. 4) Future hotspots for heat and air pollution in India, with a strategic perspective for future EWDS as well as equitable heat and air pollution mitigation and adaptation. COPE will address these research gaps by pursuing four specific objectives: (1) Identify and delineate health risks from individual and concurrent exposure to heat and air pollution in two focus cities of India – Kolkata and Delhi. (2) Build and assess the effectiveness of EWDS for exposure to heat and air pollution in two cities. The EWDS will be operationalized and provide customized alerts by accounting for specific coping and adaptive actions. (3) Uncover structural factors such as socio-cultural, economic, and behavioural factors that may contribute to reluctance or inability to comply with EWDS recommendations and investigate ways to address those. (4) Provide projections of future hotspots of co-exposure to heat and air pollution in India under alternative climate change and socioeconomic scenarios, which will act as a guidance for implementation of future EWDS along with adaptation and mitigation strategies. COPE brings together an international multidisciplinary consortium. COPE will quantify health risks in Indian settings, a low to middle income country (LMIC) experiencing more severe compounded heat and air pollution extremes that are projected to increase rapidly towards 2050. COPE will expand the scope of an existing EWS for air quality in Delhi by including exposure to heat, their concurrent exposure and health impact forecasts and evaluating its advantages, along with investigating the social and behavioural factors that impede their efficacy. COPE will extend this enhanced EWDS to the city of Kolkata. The team includes climate scientists from CICERO Center for International Climate Research (Norway), Indian Institute of Technology Delhi (IITD, India), Indian Institute of Tropical Meteorology (IITM, India) and National Science Foundation National Center for Atmospheric Research (NCAR, USA), epidemiologists at The London School of Hygiene and Tropical Medicine (LSHTM, UK), University of Queensland (UQ, Australia) and IITD, social scientists at NCAR and Environment Conservation Society -SwitchOn nongovernmental organization (SwitchON, India), and a communication team from CICERO and SwitchON. The consortium will leverage the groundwork laid by the project coordinators, which quantifies health risks associated with combined heat and air pollution exposure in Europe, as well as Delhi air quality early warning system (AQEWS) codeveloped by the partners at IITM and NCAR. COPE assesses the health risks from individual and co-exposures to heat and air pollution in Kolkata and Delhi. Daily time-series hospitalization and mortality data will be made available to formulate new exposure-response relationships (ERf) for heat and air pollution. The development of EWDS builds on the AQEWS. EWDS will generate detailed 72-hour forecasts for air pollution and heat by utilizing coupled chemistry climate models. It will use the formulated ERf to issue graded alerts regarding their potential health burden. An integrated decision support system will offer data on the factors contributing to air pollution and guidance on protective actions for heat stress management. The operationalization of the EWDS will be carried out by IITM, leveraging their position within the Ministry of Earth Sciences (MoES) and extensive expertise in developing and implementing the AQEWS. The significance of an effective EWDS lies in recognition of its benefits. COPE prioritizes active engagement and co-design with the stakeholders and user groups including vulnerable communities, health service organizations, schools, and labour unions. Through interviews, focus groups and stakeholder workshops COPE investigates socio-cultural, behavioural, and economic aspects to enhance information dissemination, understand response barriers, develop tailored risk communication, and action plans for diverse audiences, and improve coordination among stakeholders. Projections of heat stress and air quality will be made until 2050. The aim is to identify future hotspot areas where the frequencies of individual and concurrent exposure to heat/pollution in India are expected to be high. Projections will incorporate changing demographics, socioeconomic factors, GDP, and educational attainment. Results will help identifying strategic pathways for the prospective implementation of EWDS across Indian cities. Ultimately, the outcomes from the abovementioned work will converge to establish a functional EWDS designed for managing exposure to heat and air pollution and its impact on human health within LMIC settings. Communication and dissemination of the results from the project is core to obtain the objectives of the project, especially in relation to delineating health risks among vulnerable groups. COPE will have an internal communication workshop for knowledge sharing and for developing strategies for reaching out to stakeholders at different levels. COPE will maintain close collaboration with various stakeholders, including the Indian Meteorological Department (IMD), National Center for Disease Control (NCDC) under the Ministry of Health and Family Welfare (MoHFW), National Disaster Management Authority (NDMA), and the MoES, during all its phases. The Red Cross Red Crescent Climate Center will contribute to aligning project outcomes with stakeholders' and users’ needs effectively. To ensure the sustainability of the research conducted within the project's lifespan, COPE commits to providing long term support for the implemented and operational EWDS even beyond the project's conclusion.

UKRI Gateway to Research · FY 2025 · 2025-02

Malaria, caused by Plasmodium parasites, continues to be a major global health concern, with millions of cases and hundreds of thousands of deaths annually. In 2023, Brazil reported over 140,000 cases, marking it as the country with the highest malaria burden in South America. Notably, there are significant data gaps, particularly in high-risk regions such as indigenous communities and gold mining areas around the Amazon. Efforts to control malaria worldwide are further complicated by the emergence of Plasmodium drug resistance (DR), especially against artemisinin-based treatments. While resistance to artemisinin has primarily been observed in Southeast Asia, there is concern that similar issues may arise in other regions with comparable transmission dynamics, including parts of South America like the Brazilian Amazon. The generation and analysis of Plasmodium genomic data are critical for identifying DR mutations and understanding transmission patterns, including the cross-border movement of strains. Advanced genomic techniques, such as whole-genome sequencing (WGS) and targeted gene amplicon sequencing (AMP-SEQ), are used to identify species, DR mutations, and genetic diversity. Platforms like Oxford Nanopore and Illumina provide detailed clinical and epidemiological insights, thereby enhancing surveillance strategies. However, the effective utilisation of extensive genomic datasets is often hampered by a shortage of bioinformatics expertise and advanced informatics tools. Developing AI-driven informatics tools, such as the Malaria-Profiler software, is crucial for the rapid analysis and interpretation of WGS data. These tools can provide actionable insights into species identification, DR profiles, and geographic origins, which are essential for guiding clinical management, surveillance efforts, and public health interventions, particularly in data-limited regions like Brazil. Leveraging a well-established collaboration in malaria epidemiology, with extensive field site access and expertise in genomics and AI methodologies, the London School of Hygiene & Tropical Medicine (LSHTM) and the Institute of Biomedical Sciences at the University of São Paulo (ICB-USP) aim to further enhance these informatics tools. The project seeks to integrate AI models to continuously update mutation libraries and improve the predictive accuracy for species identification, DR profiling, and geographic profiling, alongside other genomic information that could support the National Malaria Control Programme (NMCP). This initiative includes conducting WGS/AMP-SEQ in Brazilian malaria hotspots to better understand genetic diversity and inform strategies for disease control and elimination in the country. The integration of AI methods with genomic data for parasite profiling has the potential to revolutionise malaria control. It enables proactive surveillance, personalised treatment strategies, and rapid responses to emerging threats, such as DR, including the identification of critical emerging Plasmodium mutations. This approach not only improves clinical care but also strengthens public health systems by facilitating informed decision-making and promoting collaborative data sharing among researchers and healthcare providers globally. The project will also involve key stakeholders, including Brazil's NMCP, to enhance capacity in AI and genomics through workshops and the development of dashboards and end-user reports. These resources will aid in implementing and validating the informatics platform, incorporating AI functionalities such as spatial analysis for public health applications. These efforts aim to ensure the tools' readiness for clinical and surveillance purposes, thereby contributing to reducing malaria and other infectious diseases in Brazil and aligning with the World Health Organization's regional elimination goals and global health objectives.

UKRI Gateway to Research · FY 2025 · 2025-02

The 'Zipime Weka Schista!' (Do self-testing sister!) study is a novel one-stop approach for improving young women's sexual and reproductive health through community-based infection screening in Zambia, a country known to have a high prevalence of HIV and cervical cancer. This novel strategy aims to integrate, in a single home visit and for the first time, self-sampling (genital and oral swabs) for the detection of multiple genital infections with serious consequences for female's sexual and reproductive health. The Zipime Weka Schista! study mainly focuses on the detection of female genital schistosomiasis (FGS), a chronic and disabling parasitic gynaecological disease that gets often confused with sexually transmitted diseases (STIs) due to their similarities in clinical presentations such as infertility, ectopic pregnancies, vaginal discharge and pain with coitus. An estimated 40 million women suffer from FGS in sub-Saharan Africa, and most of them are unaware of harbouring the disease. This is partly because the detection of FGS is challenging, as it relies on expensive equipment and expertise that are seldom available in sub-Saharan Africa, where the disease is common. Small studies have documented an increased risk of acquiring HIV and cervical cancer in women with FGS, underlying the importance of approaching diagnosis of all genital infections comprehensively and holistically, closer to the user. With over 2500 women enrolled, the Zipime Weka Schista! study constitutes the largest cohort study of a one-stop genital multi-pathogen screening in Zambia to date. Home-based self-sampling study procedures were widely accepted by the recruited participants, making this approach a feasible strategy for scaling up the integration of multi-pathogen screening, as was postulated in the initial hypothesis. Further preliminary results reveal a high prevalence of FGS and STIs including human papillomavirus (HPV) HIV and Trichomonas. The success of the first part of this UKRI Future Leaders Fellowship is a testament to the steady leadership of the FLF fellow and the strong partnership with Zambart, the overseas institution. For the second part of the FLF, the work will focus on further longitudinal investigation of long-term outcomes of the prevalent co-morbidities including cervical cancer. A sustainable screening pathway will be developed based on the laboratory and clinical results. A thorough ongoing cost-effectiveness analysis will aim to find economically feasible ways to scale up community-based programmes that will integrate the detection and care of FGS, HIV, cervical cancer and other STIs for women of reproductive age in Zambia. Results can also help inform programmes in similar settings across SSA.

UKRI Gateway to Research · FY 2025 · 2025-01

The challenge. Violent conflict has extensive repercussions that extend beyond direct fatalities and can influence well-being and human capital in many ways. The impacts of conflict, and ensuing economic and food-security crises, can disproportionately affect refugees and other vulnerable populations, especially children. A recent review on the effects of armed conflict on the health, development and education of children identified a need for future research on these outcomes over a longer life-course horizon. Unfortunately, such longitudinal research is often difficult to conduct because refugee and conflict-affected populations are often transient and difficult to follow-up. However, working with the United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA), we enriched their administrative datasets and built a unique cohort of refugee children. We can use this data, together with publicly available data on conflict, to conduct such longitudinal and longer-term research. Aims and objectives. Our proposal aims to investigate the effects of exposure to conflict on the human capital of Palestinian refugee children in Jordan, Lebanon, Syria, West Bank and Gaza. This proposed research will enable us to explore the effects of short- and long-term exposure to conflict from 2010 to 2020 on (1) family formation patterns (age at childbearing, family planning) (2) use of selected services (antenatal care, maternity care, immunizations, school attendance) (3) child well-being and development indicators (e.g. growth, school performance), and (4) all-cause mortality, including stillbirth, and risk-factors associated with early mortality (prematurity, size-for gestational-age). How will objectives be achieved: data and approach. UNRWA provides Palestinian refugees with free primary health and elementary-school services, use of which is recorded in individual-based electronic databases. Our study will use UNRWA's electronic medical and education records from nearly 1 million Palestinian refugee children which we have linked with each other and cleaned. We will join these longitudinal data with conflict-event datasets from the Uppsala Conflict Data Program (UCDP) and Armed Conflict Location & Event Data Project (ACLED). The conflict event datasets provide geospatial and time-specific conflict-related exposures. We will then use different statistical models to explore the effects of these different conflict events, conflict intensity and distance to conflict on the different refugee outcomes listed above (family formation, education and health service-use, child well-being, and child mortality outcomes). We will build a causal framework of how the timing and intensity of conflict exposures affect potential human capital outcomes using our data, and findings from the literature. Application and benefits. This information will enable UNRWA policymakers, health and education service providers, and other humanitarian actors to develop targeted interventions to ameliorate the early life course of refugee children and more effectively argue for resource allocation to specific geographic areas and demographic groups. Additionally, the study will highlight the role of healthcare and education services for affected populations and generate an evidence-base to advocate for the mitigation of conflict-related harm.

UKRI Gateway to Research · FY 2025 · 2025-01

Sexually transmitted infections (STIs) are extremely common. In Africa four easily curable STIs (chlamydia, gonorrhoea, trichomoniasis and syphilis) may affect almost one in four young people at any point in time. For most people these infections do not cause obvious symptoms but they can still be associated with important health consequences. In particular, STIs during pregnancy can have severe consequences for the outcome of the pregnancy. They are associated with a higher rate of stillbirth, babies dying shortly after birth (neonatal death), and with babies being born prematurely and at a lower birthweight. Despite these important public health consequences, control of STIs has not been suboptimal and no World Health Organization (WHO) STI control targets have been met. One reason is that currently only individuals with STI symptoms are treated for all the possible infections that can cause the symptom without specifically testing for which infection is causing the symptom-an approach called syndromic management. This approach was recommended because testing required expensive laboratory infrastructure which was not always possible in resource-constrained settings. Importantly, more than 80% of people with an STI do not have symptoms and are therefore not identified and treated. Newer diagnostic tests which do not require expensive infrastructure have become available in recent years but these tests are relatively expensive, and there is limited evidence on which population groups to target for testing and whether screening (i.e. offering testing systematically to defined groups whether or not they have symptoms) will result in health benefits. In previous work in Zimbabwe, we have shown that these diagnostic tests can be integrated into broader antenatal care. However critical data on whether using these tests improves outcomes for mothers and babies is missing. In this study we will conduct a trial to to assess if introducing screening for STIs in antenatal care compared to syndromic management results in improved outcomes for the mothers and their babies. Our study will be conducted in antenatal care clinics in Zimbabwe. We will enrol approximately 8200 pregnant women into the study. Pregnant women will be assigned by chance (randomised) to either receive standard care, where they will be treated for an STI only if they have symptoms, or to receive a test for an STI whether or not they hae symptoms, followed by treatment based on the result of that test. For each pregnancy we will collect data on important outcomes including stillbirth, prematurity and birth weight to assess if STI testing improves pregnancy outcomes. We will also collect data on the cost of using diagnostic tests in the antenatal setting and conduct a thorough evaluation of the operational and structural factors required for Ministries of Health to adopt STI testing as part of antenatal care more widely. Throughout the study we will work directly with communities to ensure the services we develop are appropriate for their needs and tackle barriers to seeking care for STIs such as stigma. We will develop a detailed plan to facilitate uptake of our study findings into local, regional and global policy, working with the Ministry of Health, WHO and other key stakeholders such as the International Union against STIs. We will also advocate with Industry for reductions in costs of tests. If successful our study will transform care for pregnant women and improve outcomes for their babies worldwide.

UKRI Gateway to Research · FY 2025 · 2025-01

In England, there are differences between people in how likely they are to catch infections. There are also differences in how ill people get when they are infected. The same groups of people are more likely to get infected and more likely to get very unwell. Those groups are people of ethnic minority backgrounds, and those groups who experience socioeconomic deprivation. There are lots of reasons why some groups are more likely to catch infections, for example because they have more social contacts because of their job, or their behaviour, or they may have different types of contact, for example if they work in a hospital or have to go there frequently for treatment. Other factors include the size of households that people live in, or the different ages of people they live with. This is important because a lot of infectious disease transmission happens in households. The reasons why people are more likely to get very unwell if they are infected are mostly because of their age and if they have an existing health condition, for example, heart disease. Some of these conditions are more common amongst people who live with socioeconomic deprivation, and amongst ethnic minority groups. Differences in health between groups of people are called health disparities, and there are lots of reasons why these differences exist, and how difficult they are to solve. What this study aims to do is understand better the health disparities and the role that infectious diseases play in creating and sustaining them. Ultimately the aim is to develop better interventions to try to decrease the health disparities that people who live with socioeconomic deprivation or ethnic minority groups experience. I will study these problems by analysing electronic health records data for over 20 million people in England. The health records are held securely on an analysis platform called OpenSAFELY, and individual patient health data is never at risk of being exposed. To add to the health records, I will use a smartphone app called Airmid to ask people about how many social contacts they have in a day and the age and occupation of their contacts. I will also use the app to ask people about how many infections they get, how severe they are, and whether they go to the GP or hospital for that infection. Collecting these data will help understand the differences seen between groups. During the project, I will analyse how infections are distributed among different groups in the population and what factors are associated with having more infections. I will look at how infections are associated with different causes of death, and if those associations are different for ethnic minority groups or those experiencing deprivation. Later in the project I will use computer models to try to understand if there are interventions that could decrease the health disparities, such as vaccination or better treatment. The project will have patient advisors involved to share their experiences and participate in the research.