Building on an existing longitudinal mental health resource in rural and urban Malawi, we will bring together national and international expertise to conduct the first large genetic association analysis of a broad anxiety measure in an African population. We will link this work to a new understanding of the lived experience of severe anxiety in highly vulnerable populations, exposed to multiple insecurities and set the foundations for a precision medicine approach to prevent and treat anxiety. We seek to (1) identify the impact of anxiety on lives and livelihoods (2) identify the correlates, antecedents and consequences of anxiety using traditional epidemiological approaches (3) understand the genetic architecture, and molecular mechanisms of anxiety, (4) identify the risk signatures in young children and adults to signpost possible disease mechanisms and for risk stratification. We will conduct repeat measures of generalised anxiety disorder and conduct qualitative research in key age groups in both rural and urban populations and work with experts in the fields of genomics and metabolomics research to build capacity in these disciplines within Malawi. We will explore the potential and acceptability of industry partnerships to ensure that future discovery using these tools includes those of African ancestry.

Conventional evaluation of new medicines is not fast enough for a pandemic. Our aim is to accelerate this process, rapidly identifying which drugs are safe and potentially effective treatments for COVID-19. AGILE is an innovative, multi-arm, multi-dose, multi-stage Phase I/IIa Bayesian adaptive platform protocol to evaluate experimental COVID-19 therapies, and to funnel plausible candidates into large Phase IIb/III trials such as RECOVERY and SOLIDARITY. We will efficiently eliminate candidates with little or no prospect of clinical success. AGILE will recruit COVID-19 patients into very early phase clinical studies, including first-in-human. The innovative design allows us to move seamlessly from first-in-human use to finding the optimal dose for COVID-19 patients. The trial is pragmatic (requiring only small numbers of patients), adaptive (so that the right drug is tested in the right group of COVID-19 patients, either in the community or in hospital) and statistically efficient (so that several drugs can be tested in parallel, making best use of a small number of patients). Our primary focus is population-scalable antiviral drugs for early treatment of COVID-19, for which we will recruit primarily in the community. AGILE has full regulatory and ethics approvals in the UK

Conduct disorder (CD) is public health challenge in Africa were rates are high. CD refers to a pattern of behavior including aggression, destruction of property, deceitfulness, theft and violation of rules. Adolescent CD is linked to high risk behaviours such as smoking, substance abuse, early sexual debut and to violent behaviours like participating in gangs, using weapons to harm, sexual coercion, and risk of arrest. In adulthood CD is associated with antisocial and violent behaviours and poor longer term health outcomes, but the pathways to these outcomes are complex, and poorly understood. Previously, we established a link between CD, Executive Functions (EFs) and violent behaviours in primary school-aged rural children. EFs are necessary for planning, problem solving and decision-making and EF impairments are linked to violence, substance misuse and risk-taking. Importantly, EFs are modifiable. This project investigates this association in early adolescence (11-13 years), a period of rapid development and escalating risk, collecting repeated measures from 1486 adolescents in urban Soweto, South Africa. We test the hypothesis that cognition, specifically deficits in EFs, underlies violent and risky behaviour amongst adolescents with CDs investigating which components of EF relate to which outcomes, and advancing a mechanistic understanding which could optimise interventions. Conduct disorders (CD) involve persistent patterns of behavior including aggression, destruction of property, deceitfulness, theft and violation of rules. Adolescent CD is linked to risk behaviours (smoking, substance use) and violent behaviours (use of weapons, sexual coercion). In adulthood they link to antisocial behaviour and are costly to society. Globally 5% of adolescents have CD; in African estimates are double that. Although difficult and expensive to treat, CD can be treated; however there is little evidence on interventions that work for adolescents. Previously, we found a link between CD and Executive Functions (EF) in younger children. EFs are mental processes important for planning, decision-making and managing frustration. EF may play an important role in violent and risky behaviour amongst CD adolescents. This project explores this link in 1486 urban adolescents in South Africa, investigating whether behavioural interventions can be enhanced by improving EF, with enormous potential for optimising behavioural interventions.

For the past several decades, global health researchers and policy-makers have raised the alarm about the growing threat that fake pharmaceuticals pose to global health. Often these concerns are framed in terms of particular places and people, for example, fake drugs from India imperil Africans’ health. We subjected these high-profile and oft-repeated claims to scrutiny. This exercise produced some unexpected findings. Across scientific, policy and popular literature, we found substantial misalignments between (1) the strength of claims about fakes alongside (2) the relative weakness of these claims’ evidence. Scientific literature in particular raised questions about apparent certainties, such as: What, exactly, are fake drugs? Are fake drugs necessarily dangerous? Where do they come from? When the global supply of life-saving medicines is beset by worries about safety, governments and citizens face difficult decisions about how to allocate scarce resources. By asking questions about these worries, we hypothesize that the problem of fake drugs is not solely a pharmacological problem; it is also a social problem. Two questions guide our project’s historical and ethnographic research 1. What accounts for the rise of fake-talk—the wide-spread and urgently-reiterated set of concerns about the dangers that fake drugs present? 2. What are the effects of fake-talk? Today, the idea that fake drugs threaten global health has become almost common-sensical. Often, these concerns are voiced in relation to how, for example, Africans’ already poor health is further imperilled by fake Indian drugs. Yet when we looked closely at the scientific literature backing up these claims, we found that they were based on unexpectedly weak evidence. This project responds to this puzzle by critically re-examining our collective common-sense about fake drugs and global health. Initial research suggests that, addition to the world of pharmacology, worries about fake drugs may be based in social worlds. When the world’s supply of live-saving drugs is beset by worries about safety, governments and citizens face difficult decisions about how to allocate scarce resources. Our project’s historical and ethnographic enquiries seek to understand the emergence and circulation of worries about fake drugs for global health, as well as to understand these worries’ effects.