- Total grants
- Total funders
- Total recipients
- Earliest award date
- 21 Jan 2017
- Latest award date
- 30 Dec 2017
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Context: Blinding corneal infections (Microbial keratitis, MK), caused by bacteria or fungi, are a major ophthalmic public health problem in low and middle-income countries. There are multiple critical issues: delayed presentation, traditional eye medicine use, limited health-worker training, limited availability and efficacy of anti-fungals, diagnostic uncertainty. Eyes are lost through progressive corneal ulceration and perforation, mediated by human and pathogen-derived proteases. Proposed Research: Randomised controlled trial (RCT) of topical chlorhexidine 0.2% vs. topical natamycin 5% for fungal keratitis. Pilot trials of chlorhexidine, a cheap and readily available antiseptic, suggest it might be at least as effective as natamycin (current standard). RCT of topical ilomastat 0.08% vs. placebo, to reduce corneal perforation from MK. Ilomastat, a potent matrix metalloproteinase inhibitor, reduced severe ulceration in animal models and earlier human clinical trials. Full-scale treatment trials are needed for translation into practice. Cluster RCT of early intervention package (topical chlorhexidine, smartphone-assisted diagnosis, treatment, referral support) vs. standard practices, to reduce blindness from MK through reducing delay between infection onset and initiating intensive treatment, with an agent covering fungi and bacteria. Evaluation of diagnostic approaches for identifying causative organism in MK (clinical, automated image-analysis, confocal microsopy, PCR) and testing potential isothermal point-of-care tests.
Infections such dengue fever, Zika and influenza generate a substantial public heath burden. It is therefore crucial to understand the biological mechanisms driving individual-level infection and immunity, and how these shape population-level epidemiological dynamics. However, such viruses can cross-react with antigenically similar pathogens, which makes it challenging to analyse immune responses and the implications for future outbreaks. This project aims to address this knowledge gap using a combination of novel mathematical methodology and empirical data. First, I plan to quantify the contribution of different biological mechanisms to observed antibody responses against arboviruses and influenza. In particular, I will combine a unique longitudinal study of dengue and Zika in Fiji with novel mathematical models to reconstruct individual infection histories, and examine potential interactions in immune responses to these viruses. The work will also generate statistical tools for next generation seroepidemiological study design. This will make it possible to perform power calculations when pathogen cross-react and/or assays lack sensitivity/specificity. Finally, I will investigate how herd immunity generated by prior infection history shapes the antigenic evolution of influenza and re-emergence of arbovirus strains. This will improve our understanding of pathogen invasion and potential for future outbreaks.
In 2012, the World Health Organization Regional Office for Europe (WHO-Europe) launched the Evidence Informed Policy Network Programme (EVIPNet-Europe) to promote evidence-informed policy-making (EIP) in its member countries. EVIPNet-Europe facilitates establishment of Knowledge Translation Platforms (KTPs) in each member country, comprised of government policy-makers. KTPs are then supported toward using evidence to design and implement national health policies. The overall aim of my Secondment Fellowship project is to evaluate EVIPNet-Europe, and by doing so contribute to knowledge on how to most effectively use research evidence to influence policy. The key goals of the project will be: To evaluate EVIPNet-Europe in selected WHO-Europe countries using a quantitative monitoring and evaluation framework. Outputs will include a report for WHO-Europe and a journal article. To qualitatively analyse the impact of EVIPNet on policy-making, identifying factors that influence this impact. I will use a case study of alcohol policy in Moldova, gathering perspectives of local policy-makers on EVIPNET’s effectiveness, acceptability and sustainability in their context. Outputs will include a report for WHO-Europe and a journal article. To gain personal experience of how research evidence is used in policy-making, and how I and other researchers can improve the impact of our research on policy.
To support the development of the WASSUP project.
STRONGER-SAFE: Understanding transmission and optimising interventions for an enhanced S.A.F.E. strategy for trachoma elimination 05 Apr 2017
Trachoma is the leading infectious cause of blindness worldwide. It is intrinsically linked to poverty in both cause and effect. Preventing blindness from trachoma has broad and profound impact on health and well-being. It is caused by repeated infection with Chlamydia trachomatis (Ct). The WHO-endorsed SAFE-Strategy aims to control infection through annual, single-dose, community-wide azithromycin treatment coupled with Water/Sanitation/Hygiene (WASH) and fly-control measures to suppress transmission. However, particularly in hyperendemic regions, the current approach is not having the anticipated impact. There are two critical issues. Firstly, current azithromycin schedules appear insufficient. Secondly, transmission routes are poorly defined and the very limited evidence-base makes it hard to focus WASH interventions and guide programmatic decisions. We propose the following: 1) Conduct intensive observation of human behaviour and hygiene practice, and fly behaviour, combined with Ct infection mapping, to identify major routes of transmission. 2) Develop and test contextually appropriate, practical, targeted WASH and fly-control approaches to interrupt Ct transmission. 3) Our modelling work indicates double-dose azithromycin two weeks apart is much more effective in controlling Ct. In a cluster-randomised trials we will test whether intensified double-dose treatment coupled with targeted transmission-interrupting strategies can control trachoma more effectively.
Despite the success of pneumococcal conjugate vaccines (PCVs) two major challenges remain. First, serotype replacement has mitigated PCV impact and pneumococci remain a predominant cause of child death. Second, PCVs are among the most expensive vaccines, which threatens sustainability in low income countries as they transition from Gavi support. The fellowship addresses those issues using a combination of epidemiological, statistical and modelling techniques and the collection of key data that leverages ongoing studies. I plan to use machine learning to unravel drivers of heterogeneity in the global serotype distribution of pneumococci, which will enable inference of pneumococcal epidemiology in settings with limited data. I will then use constrained optimisation on models that include the dynamics of serotype replacement into their predictions to inform design of more efficient PCVs that can further reduce the global pneumococcal diseases burden. I further plan to use a set of novel models to estimate who infects infants, a key knowledge gap in the assessment of reduced dose PCV schedules, an approach being pursued as a potential cost saving strategy. Phylogenetic inference in combination with mathematical models will be used to identify common transmission pathways to infants and risk factors associated with them.
Core costs and office rent for a branch of a charity supporting the bereaved.
Grant to Volunteering Matters 11 May 2017
£135,000 over three years (3 x £45,000) for the salary, project delivery and support costs of an Inclusion Worker engaging young disabled people in volunteering.
Healthcare markets in low- and middle-income countries (LMICS) are undergoing dramatic change, with private sector expansion, emergence of new organisational forms and business models, and growing foreign investment. The regulation systems in these countries are inadequate and ill-suited to manage these challenges and future market evolution, and rarely incorporate modern perspectives on regulation which highlight the need for "responsive", "smart" and risk-based regulation, drawing on an expanded range of regulatory strategies, tools and actors. We aim to understand the challenges that recent developments in LMIC healthcare markets pose for effective regulation. We will review recent trends in private sector development and regulation systems in 3 LMICs with rapidly changing healthcare markets. We will assemble a group of scholars and policymakers with expertise in regulatory theory and implementation in a set of middle- and high income countries. We will debate appropriate theoretical frameworks and methods for studying regulatory developments, and consider what concepts and lessons might be relevant to LMICs (taking into account differences in resources, institutions, health systems, and history) and identify critical research questions. Outputs will be a network of scholars, an agenda setting paper, and a proposal for a larger scale project to take these ideas forward.
Development of an early intervention to support babies with Congenital Zika Syndrome and their families 15 May 2017
On February 1, 2016, Zika virus (ZIKV) was designated as a Public Health Emergency of International Concern by the WHO. ZIKV has now spread to 72 countries and territories, including in Asia, Africa and the Americas. It is now clear that congenital infection with ZIKV in the first trimester can cause microcephaly, and these cases have already been reported in 20 countries. In Brazil, there are 2975 cases of microcephaly suspected of being related to ZIKV . Congenital infection with ZIKV is also linked to other congenital abnormalities, besides microcephaly, including: neurological conditions , ophthalmic abnormalities , hearing loss and bone and joint disorders . Congenital Zika Syndrome therefore extends beyond microcephaly alone. The full spectrum of conditions is not yet known, nor is there an accurate estimate of prevalence of Congenital Zika Syndrome. Congenital Rubella and CMV infection also cause neurological sequelae, including microcephaly, and for these conditions there are approximately twice as many children born with other impairments than those born with microcephaly. , Congenital Zika Syndrome is therefore likely to be at least twice as common as microcephaly alone.
A platform for the transgenic modification of Sandflies (Lutzomyia longipalpis) and Triatomine bugs (Rhodnius prolixus) towards deriving insect vectors refractory to disease agents mediated by CRISPR-Cas9 gene drive 05 Sep 2017
Vector borne pathogens Leishmania, and Trypanosoma cruzi cause devastating human disease (Leishmaniasis and Chagas disease respectively). We contribute to a new strategy by genetically modifying insect vectors, sandflies (Lutzomyia longipalpis) and triatomine bugs (Rhodnius prolixus), leading eventually to transgenic insects resistant to disease agents. We will use two different transgenic approaches, piggyBac and CRISPR-Cas9. PiggyBac is a method for semi random insertion of exogenous DNA into the genome. CRISPR-Cas9 is a new and highly targeted method to manipulate genes in a manner not previously possible. Microinjection of insect embryos with piggyBac plasmids to obtain insects expressing fluorescent markers for subsequent CRISPR-Cas9 knockout experiments facilitating easy monitoring of outcomes. Knockout of fluorescent markers (above), using CRISPR-Cas9 constructs, demonstrating that system components are functional and that we can precisely target genes of interest. Knockout of endogenous genes by CRISPR-Cas 9 that are non-essential or important in sustaining infection in insect vectors. Insertion and expression of exogenous DNA (fluoresence markers) using CRISPR-Cas9 harnessing homology directed repair facilitating inheritance to offspring at levels above mendelian inheritance (gene drive). Pilot outputs offer real prospects for developing powerful approaches of interrupting disease transmission.
E cigarettes:history, evidence and policy 30 Sep 2017
The role and regulation of electronic cigarettes is currently a matter of widespread public and policy debate . Forms of regulation have varied by country even though the scientific research is common to all countries . What has led to this disjuncture between science and policy? This project builds on existing discussion and preliminary examinations of the subject from the three initial collaborating countries, the UK, the US and Australia. These three countries have taken a different national stance to e cigarettes regulation and harm reduction through nicotine. Our hypothesis is that these divergences build on historical differences between the 3 countries over tobacco and in health policy more generally. Our key goals are: 1.To undertake outline research in the three countries according to a common format to examine the recent science policy relationship in the area of e cigarettes . 2. To hold a workshop in the UK involving public health interests and policy makers involved with e cigarettes to feed into the research. 3.To hold a meeting of country participants in London to discuss research outlines, develop an initial publication and a plan for a funded programme of comparative historical policy research in a wider range of countries.