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      "title_narrative":["Evaluating multiple loci modulating susceptibility of African malaria parasites to artemisinin"],
      "description_narrative":["Combination drugs for treatment of malaria deployed globally since the start of the 21st century have provided a substantial public health benefit. Malaria deaths across Africa in particular have plummeted since a peak in the 1990s, when failure of the drugs chloroquine and sulphadoxine-pyrimethamine precipitated a rise in infant and child deaths. A key component in all the currently effective drug combinations is the plant-derived chemical called artemisinin. The parasite-killing ability of artemisinin has recently been threatened by the emergence of reduced susceptibility in the Mekong region: this is manifest as a slowing of artemisinin clearance of P. falciparum from the blood of treated malaria patients. Although under combination treatments these patients should eventually experience a full cure in most cases, in this region the combination partner drugs are also failing in some patients. Careful monitoring and vigilance of malaria drug resistance is therefore needed. A parasite gene has been identified in Cambodia and the surrounding region which contributes to the loss of effectiveness of the artemisinin drug - this gene, which encodes a kelch-domain protein and is called K13, has accumulated a variety of mutations. These are strongly associated with the loss of effectiveness of artemisinin against these parasites. However, this same phenomenon has not yet been observed in African malaria parasites - in the small number of cases where drug treatment does not work, K13 mutations are not implicated as the cause.     In the past 2 years, gene-editing studies by ourselves and others have successfully demonstrated a direct effect of 3 genes in reducing susceptibility to artemisinin : pfap2mu, pfubp1 and pfcoronin. Variants of these genes elicit increased parasite survival in vitro in the ring-stage artemisinin survival assay (RSA). In the case of trafficking adaptor potein subunit AP-2mu, we have shown that the role of this protein in P. falciparum is unlike in other organisms as it does not interact with clathrin, but is associated with an as yet unknown compartment in the cell that appears to also contain K13, although we found no evidence of direct interaction between AP-2mu  and the K13 protein. There is, however, good evidence of direct interaction of AP-2mu with a different kelch protein , K10. Polymorphisms in the gene encoding the K10 protein have been previously identified as a genetic component of parasites from the Mekong region in which the K13-dependent reduced artemisinin susceptibility originally arose. This work was carried out by PhD student Ryan Henrici, who completed his doctoral studies in 2018 and has moved on.   We now request support to extend this work, using gene editing to test the effect of new mutations. In preliminary studies of both field samples and UK isolates, we have already identified a number of such new mutations in our current five genes of interest - pfk13, pfap2mu, pfubp1, pfcoronin and pfk10 (see Case for Support). For each new isolate (either from the UK or from our collaborator Dr Bismarck Dinko in Ho, Ghana) that is adapted to culture, we will fully test drug susceptibility, and genetically characterise them using genome sequencing. In gene-editing experiments we will then directly measure the impact of each candidate gene variant in both established laboratory lines and in our new cultures from UK and Ghanaian patients; any variant proven to generate a drug susceptibility phenotype may therefore be contributing to changing patterns of drug susceptibility, and could be developed as a surveillance marker for use in malaria endemic areas. Our work will thus assist our understanding of resistance to our current combination drugs, and help us to devise strategies for deploying these drugs carefully in both the UK and Africa, to maximise their useful life in curing malaria patients.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "default_lang":"en",
      "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_R005990_1",
      "reporting_org_ref":"GB-GOV-13",
      "reporting_org_type_code":"10",
      "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"],
      "title_narrative":["IMPRINT: IMmunising PRegnant women and INfants neTwork"],
      "description_narrative":["Far too many newborns continue to die in early life, particularly in low-and middle income countries (LMIC). Many die from infections, some of which could be prevented. During the late stages of pregnancy, antibody is transferred across the placenta from mother to child, providing protection to the infant in the early weeks of life. However, if the mother has insufficient protection against certain infections, the infant will also not be protected.   Vaccinating women in pregnancy can enhance the level of antibody in the mother, thereby protecting the mother, and increasing the amount of antibody transferred across the placenta - protecting the infant from birth too. This concept has already been successfully established for the prevention of tetanus, influenza and pertussis (whooping cough). Many investigators and stakeholders are interested in using this strategy to protect infants from other serious infections, for example group B streptococcus or respiratory syncytial virus (RSV), and vaccines against these infections are in development. Some fundamental gaps in our understanding remain about the immune response to vaccines in pregnancy and in newborn infants which are essential for us to address in order to accelerate development of new vaccines. It is also very important that the scientific community tackles how best to implement such vaccine programmes in both high-income countries and LMIC.   Our unique inter-disciplinary network represents stakeholders from basic science, immunology, vaccinology, social sciences, industry, public health and national and international policy makers who have come together in order to tackle the key challenges in the best use of vaccines in pregnancy and in newborns, and in the long term, improve maternal and newborn health.     Specifically, the IMPRINT network will implement collaborative research projects to answer fundamental biological questions about antibody transfer of antibody across the placenta, how to induce the \"best\" antibody, and its effect on the maturing newborn immune system. We will investigate if maternal vaccines interfere with the way in which the baby responds to vaccines later in infancy and childhood, to ensure that protection is not compromised at any stage. Co-factors such as nutrition or other infections might also change the way in which mothers and infants are protected by vaccines. Hence we need to take them into consideration if we are to ensure optimal protection of vaccines in pregnancy and early life. We will also find out why women decide to receive or not to accept vaccines in different countries in order to optimise the uptake of current and new vaccines. We will endeavour to work out how vaccine safety and effectiveness  can be best monitored, given the different health care systems in different countries. Addressing these implementation challenges will enable us to better understand the issues and site-preparedness in the many geographical areas and populations in which IMPRINT investigators work.    IMPRINT is a multi-disciplinary network linking investigators in Europe, Africa and Asia and can therefore address these questions comprehensively. We are uniquely set up to investigate these challenges through the diversity of expertise, availability of samples and datasets already available through our collaboration, which the members are happy to share. Through our network, we will train researchers in LMIC to take forward these important questions, and we will be the forum to provide the best evidence for the safe and efficient use of vaccines in pregnancy and newborns for the ultimate goal of lowering maternal and newborn deaths from infections.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
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      "default_currency":"GBP",
      "default_lang":"en",
      "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_R019177_1",
      "reporting_org_ref":"GB-GOV-13",
      "reporting_org_type_code":"10",
      "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"],
      "title_narrative":["MICA: Creating an open access knowledge hub of nutritional biomarkers for use in global health settings"],
      "description_narrative":["Malnutrition, from either under- or over-nutrition, directly affects one in three people globally making malnutrition, together with diet, by far the biggest risk factors for the global burden of disease. Widespread undernutrition and micronutrient deficiencies lead to poor child growth, impaired mental development and reduced adult labour productivity, while a transition towards a more 'westernised' diet is associated with rising rates of obesity and diet related non-communicable diseases. This under- and over-nutrition often coexists to create a 'double-burden' of malnutrition-related health consequences and, with rapid urbanization and the associated nutrition transition, this double burden is most predominant in many low- and middle-income countries (LMICs).   To advance understanding of links between diet, nutrition and health in LMICs and to develop and evaluate evidence-based programmes and policies, detailed understanding of nutritional status is required. Existing, community-based studies and surveys from LMIC settings often lack detailed data on individual and population-level nutritional status to inform on policy. Data from critical population categories (e.g. infants, children, adolescents, pregnant and lactation women) are often limited to anthropometry and easy-to-assay parameters (e.g. haemoglobin) or single micronutrients (e.g. vitamin A, iodine). This leads to a knowledge gap to describe the nutritional vulnerabilities in these population groups and hence inform on the design of novel interventions.  Modern methods to measure nutritional status have moved away from single nutrient assays requiring relatively large aliquots of blood, access to sample storage facilities, and sophisticated equipment towards 'multiplex' approaches where groups of analytes can be measured in small volumes or on more appropriate matrices, such as dried blood spots. A critical barrier to applying these novel methodologies in LMIC contexts is a lack of easy to access information on their availability and utility and a lack of technical support for the required platforms.  In response to this global need, the aim of this application is to bring together expertise in nutritional biomarkers, to create a freely available, online resource (a 'knowledge hub') to support the accurate and detailed assessment of nutritional status in populations from low- and middle-income countries (LMICs). Through a network of academic and industry experts, we will also identify research gaps, where existing methodologies are not practical for implementation in low resource settings or for use in large, population based research in LMICs. The knowledge hub created will enable and support all nutrition and health related research activities in LMICs contributing towards a greater depth of knowledge on the nutritional status of populations in these settings. The longer-term vision of this work is to establish centres of excellence in nutritional assessment methodologies in LMIC settings. Supported by a network of academic, technical and industry experts, these centres will support academic and programmatic research in LMICs, enabling a more comprehensive understanding of the relationship between diet, nutrition and health. Further, where research gaps are identified, we will work with academic and industry partners to develop novel assays to meet the research needs for nutrition and health research globally.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
      "participating_org_ref":["GB-GOV-13","GB-COH-RC000346","GB-COH-RC000346","GB-COH-RC000297"],
      "participating_org_role":["1","2","3","4"],
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      "participating_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY","MEDICAL RESEARCH COUNCIL","MEDICAL RESEARCH COUNCIL","KING'S COLLEGE LONDON"],
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      "contact_info_organisation_narrative":["Department of Business Energy and Industrial Strategy"],
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      "contact_info_email":["enquiries@odamanagement.org"],
      "contact_info_website":["https://www.gov.uk/government/publications/beis-official-development-assistance-research-and-innovation"],
      "contact_info_mailing_address_narrative":["Department of Business, Energy and Industrial Strategy, 4th Floor, 1 Victoria Street, SW1H 0ET"],
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      "recipient_country_code":["BD","IN","TH","BR"],
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      "budget_type":["1"],
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      "budget_period_end_iso_date":["2019-03-31T00:00:00Z"],
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      "budget_value_currency":["GBP"],
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      "default_currency":"GBP",
      "default_lang":"en",
      "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_R014922_1",
      "reporting_org_ref":"GB-GOV-13",
      "reporting_org_type_code":"10",
      "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"],
      "title_narrative":["One Health Drivers of Antibacterial Resistance in Thailand"],
      "description_narrative":["Like many Overseas Development Assistance (ODA) countries, and particularly those in South and South East Asia, Health and well-being in Thailand is significantly undermined by the high prevalence of antibacterial drug resistance (ABR) in disease-causing bacteria found in humans, animals and the environment. ABR reduces the ability of doctors to treat infections with antibiotics and other antibacterial drugs, with an estimated impact on Thailand in 2010 of 38,000 deaths and an economic loss of 1.2 billion US$. ABR rates continue to rise and its impact is rising in parallel.  Because of the threat of ABR, the Thai National Strategic Plan on Antimicrobial Resistance (2017-2022) has been instigated. This will involve improved national surveillance for ABR bacteria to quantify the problem, initiatives to reduce the rates of infections and those to reduce the usage of antibiotics and other antibacterial drugs, which are known to select for ABR bacteria. However, even when this strategic plan starts to pay dividends, there will be much still to learn about ABR in Thailand, and in other ODA countries, as is also true for developed countries where ABR reduction strategies have been in place for some time.  In this development project, we will build on partnerships we have already initiated between UK and Thai clinicians and academics. We will develop a consortium grant application to address knowledge gaps about ABR in Thailand, which we have identified through discussions between UK and Thai partners. The consortium will consider whether chemicals in the environment - present naturally or as a result of agricultural pollution (e.g. herbicide use) - can select for ABR bacteria. This would render strategies to reduce antibiotic use less effective in reducing ABR in a community where chemical pollution of the environment is common. We will also consider whether ABR bacteria circulate within local environments in rural Thailand, and will measure how this changes over time as the Thai National Strategic Plan on Antimicrobial Resistance progresses. We will perform research aimed at understanding key behaviours around antibiotic use by farmers, farm management practices, and how people make decisions around healthcare. We will use the information that we generate from the microbiology, genomic and chemical screens and the anthropological research to produce mathematical models that can be used to predict useful changes that can be made to reduce ABR in Thailand and other ODA countries. We will also help Thai policymakers  evaluate the effectiveness of changes initiated through the Thai National Strategic Plan. Finally, we will develop technologies that will be used to streamline our research; technologies that may also be useful to help local communities tackle the problem of ABR.  During the development project we will run a series of workshops in Thailand, which will be used to develop the details of our proposed research project and to identify the study sites we will use. These workshops will also give us the opportunity to share knowledge amongst Thai and UK ABR experts, and bring together a group of early career academics, to raise the knowledge base around ABR in Thailand. We will also discuss postgraduate education strategies, and public engagement events in Thailand. The development phase will also involve a comprehensive investigation of policymaking around ABR in Thailand, enabling us to tailor our consortium research project to the needs and knowledge gaps  of these groups and individuals","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
      "participating_org_ref":["GB-GOV-13","GB-COH-RC000346","GB-COH-RC000346"],
      "participating_org_role":["1","2","3","4"],
      "participating_org_type":["10","15","15","80"],
      "participating_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY","MEDICAL RESEARCH COUNCIL","MEDICAL RESEARCH COUNCIL","UNIVERSITY OF BRISTOL"],
      "activity_status_code":"4",
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      "contact_info_organisation_narrative":["Department of Business Energy and Industrial Strategy"],
      "contact_info_department_narrative":["General enquiries"],
      "contact_info_email":["enquiries@odamanagement.org"],
      "contact_info_website":["https://www.gov.uk/government/publications/beis-official-development-assistance-research-and-innovation"],
      "contact_info_mailing_address_narrative":["Department of Business, Energy and Industrial Strategy, 4th Floor, 1 Victoria Street, SW1H 0ET"],
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      "default_lang":"en",
      "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_S004769_1",
      "reporting_org_ref":"GB-GOV-13",
      "reporting_org_type_code":"10",
      "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"],
      "title_narrative":["One Health Drivers of Antibacterial Resistance in Thailand"],
      "description_narrative":["Antibacterial Resistance (ABR) is a significant source of excess mortality in Overseas Development Assistance (ODA) countries and constitutes a major, increasing threat to wellbeing and economic development. Antimicrobial Resistance (AMR), predominantly ABR, is estimated to have caused 38,000 deaths and an economic loss of 1.2 billion US$ in Thailand in 2010. Because of good record keeping and surveillance, Thailand has been used as an exemplar for characteristics of ABR in ODA countries. ABR is common in human, environmental and animal bacterial isolates. However, ABR has mostly been studied separately in discrete sectors (e.g. hospital patients or poultry). The key drivers of ABR relevant to human health cannot be pinpointed in this way because the selection and transmission of ABR results from interactions between humans, animals, and the environment. A \"One Health\" approach to the problem is required.  During this consortium project, we will study the Enterobacteriaceae family bacteria Klebsiella pneumoniae (Kp) and Escherichia coli (Ec), which reside in the human and animal gut, are common in environments contaminated with faeces, are are considered a significant threat to human health in Thailand. They are commonly carbapenem- and/or 3rd-generation cephalosporin-resistant (3GCR), which are drugs commonly used for serious infections. Carbapenem-resistant Enterobacteriaceae (CRE) are also recognised by WHO as one of the highest priority pathogens globally for which new ABs are urgently needed. Ec and Kp cause a range of infections in hospitalized patients (e.g. surgical site, intra-abdominal, pneumonia, sepsis) and serious community-acquired infections (e.g. complicated urinary tract infection, pyogenic liver abscess, meningitis). The prevalence of 3GCR Kp and Ec in human infections in Thailand has been increasing from less than 10% in 1999 to 50% in 2016, and of carbapenem-resistant Kp from none prior to 2010 to 10%-20% in 2016.  Our consortium's vision is to build a holistic picture of the drivers of ABR in Thailand and to use this information to benefit the Thai people, and as an exemplar for other ODA countries.  The term \"driver\" may refer to: 1) a material condition or substance, such as a chemical (e.g. an Antibiotic), which, at a particular concentration, selects for the increased prevalence of ABR bacteria; 2) an action, such as exposing bacteria to that chemical by taking an antibiotic; or 3) a socioeconomic condition or circumstance which accounts for that action (e.g. the economic necessity to keep working in the face of illness). A full understanding of ABR drivers at every level is important for the design of effective and appropriate interventions to limit ABR. Hence, this interdisciplinary consortium will investigate them all.  Our study area will be the Mae Klong-Ta Chin Basin, which covers an area of 80x80 km in the central and western part of Thailand. This is the area where the Mae Klong and Ta Chin rivers run from their mountain sources along the Thai-Myanmar border (Mae Klong river) and upper central Thailand (Ta Chin river) down to the Gulf of Thailand. The study area includes districts spread over five provinces (Karnchanaburi, Ratchaburi, Samut Songkram, Samut Sakorn and Nakornprathom). Both rivers enter the study site and run through areas where there are numerous factories, animal farms, rice fields, fruit orchards and communities, allowing multiple possible drivers to be considered in our work.  Our work will run alongside Thailand's National Strategic Plan on AMR, giving us a perfect opportunity to embed our findings in annual reviews of the Strategic Plan, influencing policy and having a relatively short term and direct impact on human health in Thailand. Our engagement and stakeholder activities will also facilitate dissemination of our findings into other countries within the same global region, and comparisons with other projects across the globe will yield added value.","The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world."],
      "participating_org_ref":["GB-GOV-13","GB-COH-RC000346","GB-COH-RC000346"],
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      "participating_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY","MEDICAL RESEARCH COUNCIL","MEDICAL RESEARCH COUNCIL","UNIVERSITY OF BRISTOL"],
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      "contact_info_email":["enquiries@odamanagement.org"],
      "contact_info_website":["https://www.gov.uk/government/publications/beis-official-development-assistance-research-and-innovation"],
      "contact_info_mailing_address_narrative":["Department of Business, Energy and Industrial Strategy, 4th Floor, 1 Victoria Street, SW1H 0ET"],
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