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Insecticides work by killing mosquitoes that can transmit malaria and have been extremely successful in reducing malaria cases throughout sub-Saharan Africa. However, mosquitos are increasingly resistant to insecticides, threatening to reduce their effectiveness. Despite the gravity of this impending threat, the extent of insecticide resistance (IR) and its consequences for public health remain poorly understood. A fundamental assumption is that resistant mosquitoes are identical to susceptible ones in all aspects other than their response to insecticides. However, there are several reasons why this may not be the case. For example, malaria transmission is known to be more sensitive to variation in the long-term survival and behaviour of mosquitoes than to their overall abundance. These features, in addition to other mosquito life-history traits such as their reproductive success, may be altered in resistant mosquitoes. Together this could result in insecticide-based control methods retaining a higher than expected degree of efficacy, even in areas where IR levels are high, which would suggest the possibility of developing control methods to mitigate the consequences of resistance i.e. \"resistance busting strategies\". Thus understanding the ecology and behaviour of IR mosquitoes and how their life history is affected in the short and long-term by control measures is crucial for prediction of the consequences of resistance. Unfortunately, these parameters are difficult to directly measure under natural field conditions, and may be poorly reflected in laboratory bioassays. However, recent developments in ecological modelling have delivered breakthrough, but as yet rarely applied, methods for deriving such hidden (latent) information from the multiple types of data that are routinely collected in mosquito surveillance. I propose to use these new methods to investigate the population dynamics and ecology of malaria mosquitoes in an area of high IR, and to quantify the impacts of both traditional and novel control methods on mosquito life history under field operational conditions. I will focus on the Banfora district of Burkina Faso, a region of high IR, and will make use of mosquito surveillance data, including mosquito abundance, infectiousness, IR status and behaviour, being collected by my collaborators in the AvecNet programme. This data collection is part of a 2-year 90-villages large-scale intervention trial of two alternative malaria control methods for which laboratory assays predict will reduce mosquito populations through two different routes: 1) traditional bednets (LLIN) that are coated with the insecticide pyrethroid, which works by killing adult female mosquitos; and 2) new Olyset DUO nets that are coated with a pyrethroid to reduce adult mosquito survival but also with pyriproxifen, an insect juvenile hormone that affects fecundity and longevity. However, it is unclear how reliably these expected demographic impacts occur when applied within natural populations. To address these issues I will apply novel analytical tools that integrate the various types of data generated from widely-used surveillance techniques with clinical incidence data, in order to reconstruct the hidden population dynamics and life history-traits of IR mosquito vectors, and use it to 1) determine how the ecology of IR mosquitoes modulates their malaria transmission potential, 2) quantify the impacts of current and novel control methods on these mosquitoes and 3) design optimal deployment of future intervention methods in areas of high IR.","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 GLASGOW"], "activity_status_code":"4", "activity_date_iso_date":["2016-05-01T00:00:00Z","2016-07-01T00:00:00Z","2019-04-30T00:00:00Z","2019-06-30T00:00:00Z"], "activity_date_type":["1","2","3","4"], "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"], "activity_scope_code":"4", "recipient_country_code":["BF"], "recipient_country_percentage":[100.0], "sector_code":["12182"], "sector_vocabulary":["1"], "policy_marker_code":["1","5","6","7","8","10","11","12"], "policy_marker_significance":["0","0","0","0","0","2","0","0"], "policy_marker_vocabulary":["1","1","1","1","1","1","1","1"], "collaboration_type_code":"1", "default_flow_type_code":"10", "default_finance_type_code":"110", "default_aid_type_code":["D02"], "default_tied_status_code":"5", "budget_status":["1","1","1"], "budget_type":["1","1","1"], "budget_period_start_iso_date":["2016-04-01T00:00:00Z","2017-04-01T00:00:00Z","2018-04-01T00:00:00Z"], "budget_period_end_iso_date":["2017-03-31T00:00:00Z","2018-03-31T00:00:00Z","2019-03-31T00:00:00Z"], "budget_value":[72685.35,97633.03,98423.85], "budget_value_currency":["GBP","GBP","GBP"], "capital_spend_percentage":0.0, "transaction_type":["3","3","3","3","3","3","3","3","3","3","3","3","2"], "transaction_date_iso_date":["2019-09-30T00:00:00Z","2019-03-31T00:00:00Z","2018-12-31T00:00:00Z","2018-09-30T00:00:00Z","2018-06-30T00:00:00Z","2018-03-31T00:00:00Z","2017-12-31T00:00:00Z","2017-09-30T00:00:00Z","2017-06-30T00:00:00Z","2017-03-31T00:00:00Z","2016-12-31T00:00:00Z","2016-09-30T00:00:00Z","2016-05-01T00:00:00Z"], "transaction_value":[24755.12,24755.13,24556.24,24556.24,24556.24,24556.24,24358.93,24358.93,24358.93,24358.93,24163.21,24163.21,293497.35], "transaction_value_currency":["GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP"], "transaction_value_date":["2019-09-30T00:00:00Z","2019-03-31T00:00:00Z","2018-12-31T00:00:00Z","2018-09-30T00:00:00Z","2018-06-30T00:00:00Z","2018-03-31T00:00:00Z","2017-12-31T00:00:00Z","2017-09-30T00:00:00Z","2017-06-30T00:00:00Z","2017-03-31T00:00:00Z","2016-12-31T00:00:00Z","2016-09-30T00:00:00Z","2016-05-01T00:00:00Z"], "hierarchy":1, "transaction_value_usd":[30599.764129366195,32602.63128151429,31129.376362648964,32074.474764832852,32638.51205124945,34305.26633811277,32651.312156137043,32465.7521476647,31183.499559936587,30042.87106980025,30194.648397889665,31751.372809769164,426472.40317648376] },{ "default_currency":"GBP", "default_lang":"en", "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_P006876_1", "reporting_org_ref":"GB-GOV-13", "reporting_org_type_code":"10", "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"], "title_narrative":["A comparative trial of seasonal vaccination with the malaria vaccine RTS,S/AS01, seasonal malaria chemoprevention and the two interventions combined"], "description_narrative":["There has been substantial progress in the control of malaria during the past decade, but it is estimated that in 2015 there were still 438 000 deaths from malaria, despite widespread deployment of insecticide treated bednets and an increase in access to diagnosis and effective treatment: new tools and approaches are needed. In the African Sahel and sub-Sahel, the risk of malaria is concentrated in the few months of the rainy season, although some transmission continues during the rest of the year. The seasonality of malaria in this part of Africa has allowed the development of a control measure called seasonal malaria chemoprevention (SMC), which involves treatment of young children, regardless of whether they have any symptoms, with the antimalarials sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) at monthly intervals on four occasions during the malaria transmission season, a regimen which is very demanding on health care givers and recipient children. The malaria vaccine RTS,S/AS01 has been in development for over 20 years. A recent trial conducted in 15,439 children showed that when three doses of the vaccine were given to children aged 5-17 months, followed by a fourth dose a year later, the vaccine provided 37% protection against clinical attacks of malaria over a period of 4 years, and a similar level of protection against severe malaria. The vaccine caused febrile convulsions in about 1% of children and there was a small, unexplained, increase in the incidence of meningitis in vaccine recipients. These findings were reviewed by the European Medicine Agency in July 2015 and, based on the balance of benefits and risks, the Agency gave the vaccine a positive opinion. WHO has subsequently recommended that several large pilot implementation studies should be done before the vaccine is deployed more widely and that alternative approaches to its delivery should be explored. A characteristic feature of the vaccine is that it produces high levels of protection in the first few months after vaccination but that this subsequently wanes. Vaccine efficacy of 86% (26/30 subjects protected) was obtained in a recent trial in USA military volunteers challenged shortly after three doses of vaccine had been given, the last dose at a lower concentration than usual. The aim of this study is to take advantage of the high initial efficacy of RTS,S/AS01 to investigate its potential to provide protection to children exposed to malaria for just a few months each year. A three arm trial is proposed which will compare (a) administration of three doses of RTS,S/AS01 to young children followed by a fourth and a fifth dose at the beginning of two subsequent malaria transmission season (b) administration of SMC with SP + AQ as recommended by WHO (c) the combination of these two interventions. The main objectives of the trial will be to determine whether RTS,S/AS01 provides a similar level of protection to that of SMC and is equally cost effective as SMC but is easier to administer and whether combination of the two interventions provides an added, cost effective benefit. The trial will be conducted in 6,000 children (2,000 in each arm) in Hounde, Burkina Faso and Bougouni, Mali where a trial of adding the antibiotic azithromycin to the anti-malaria treatment regimen used for SMC is currently under way and due to finish at the end of 2016. The study team and many of the techniques needed for the new trial are, therefore, in place. The main end-point of the new trial will be the incidence of episodes of clinical malaria severe enough to warrant treatment. Other end-points will be the incidence of severe malaria, hospital admissions with malaria and anaemia. The safety of the two interventions will be monitored, with a focus on meningitis. The costs of the two approaches and of the combination will be measured and the preference of the local populations for each intervention will be determined.","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","LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE"], "activity_status_code":"4", "activity_date_iso_date":["2016-10-01T00:00:00Z","2016-10-01T00:00:00Z","2020-06-30T00:00:00Z","2020-06-30T00:00:00Z"], "activity_date_type":["1","2","3","4"], "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"], "activity_scope_code":"2", "recipient_country_code":["BF","ML"], "recipient_country_percentage":[50.0,50.0], "sector_code":["12182"], "sector_vocabulary":["1"], "policy_marker_code":["1","5","6","7","8","10","11","12"], "policy_marker_significance":["0","0","0","0","0","0","0","0"], "policy_marker_vocabulary":["1","1","1","1","1","1","1","1"], "collaboration_type_code":"1", "default_flow_type_code":"10", "default_finance_type_code":"110", "default_aid_type_code":["D02"], "default_tied_status_code":"5", "budget_status":["1","1","1","1"], "budget_type":["1","1","1","1"], "budget_period_start_iso_date":["2016-04-01T00:00:00Z","2017-04-01T00:00:00Z","2018-04-01T00:00:00Z","2019-04-01T00:00:00Z"], "budget_period_end_iso_date":["2017-03-31T00:00:00Z","2018-03-31T00:00:00Z","2019-03-31T00:00:00Z","2020-03-31T00:00:00Z"], "budget_value":[417057.4,837472.76,953729.4,1070040.7], "budget_value_currency":["GBP","GBP","GBP","GBP"], "capital_spend_percentage":0.0, "transaction_type":["3","3","3","3","3","3","3","3","3","3","3","3","3","3","2"], "transaction_date_iso_date":["2020-12-31T00:00:00Z","2020-03-31T00:00:00Z","2019-12-31T00:00:00Z","2019-09-30T00:00:00Z","2019-06-30T00:00:00Z","2019-03-31T00:00:00Z","2018-12-31T00:00:00Z","2018-09-30T00:00:00Z","2018-06-30T00:00:00Z","2018-03-31T00:00:00Z","2017-12-31T00:00:00Z","2017-09-30T00:00:00Z","2017-06-30T00:00:00Z","2017-03-31T00:00:00Z","2016-10-01T00:00:00Z"], "transaction_value":[14152.14,53672.67,53672.67,53331.4,53331.4,53331.4,53331.4,42041.54,42041.54,42041.54,42041.54,41705.74,41705.74,83411.48,3491906.36], "transaction_value_currency":["GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP"], "transaction_value_date":["2020-12-31T00:00:00Z","2020-03-31T00:00:00Z","2019-12-31T00:00:00Z","2019-09-30T00:00:00Z","2019-06-30T00:00:00Z","2019-03-31T00:00:00Z","2018-12-31T00:00:00Z","2018-09-30T00:00:00Z","2018-06-30T00:00:00Z","2018-03-31T00:00:00Z","2017-12-31T00:00:00Z","2017-09-30T00:00:00Z","2017-06-30T00:00:00Z","2017-03-31T00:00:00Z","2016-10-01T00:00:00Z"], "hierarchy":1, "transaction_value_usd":[18928.32693287648,66422.59578733049,70472.04165773519,65922.85800629851,67607.27785830628,70237.72324875495,67606.97983677374,54913.142802184324,55878.8035115753,58732.37217767954,56353.519882224784,55585.70175188095,53390.3141450314,102874.81179925479,4309978.118524091] },{ "default_currency":"GBP", "default_lang":"en", "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_P022081_1", "reporting_org_ref":"GB-GOV-13", "reporting_org_type_code":"10", "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"], "title_narrative":["A mathematical modeling framework for tuberculosis burden estimation and economic evaluation of pharmaceutical interventions"], "description_narrative":["Tuberculosis (TB) is a major cause of disease and death globally. In 2015, WHO estimated there were 9.6 million TB cases and 1.5 TB deaths. Nearly 500,000 of these cases were resistant to two or more of the main drugs used to treat TB. New drugs, and combinations of drugs, are being developed to treat tuberculosis, as are new vaccines that may protect against disease in adults. Quantifying the burden of TB is fundamental to understanding its global epidemiology and for making appropriate resource allocation decisions. Most estimates of new TB case numbers each year rely strongly on the number of cases reported by countries in that year to WHO. Unfortunately, one in three TB cases are thought to go either undetected or unreported, so the number of cases reported underestimates the number of new cases. While one can correct for this, it is hard to know exactly how much to adjust the reported numbers. Some countries have good systems for recording causes of deaths, which can be used to estimate the number of deaths caused by TB. Increasingly, large and expensive prevalence surveys are being used to estimate the number of people with active disease in a population. These estimates are less subject to bias, but measure a different quantity. Little work has explored the best way of combining these three data sources. A major goal of this work is to use mathematical transmission models for burden estimation and provide a unified framework for all data. These models yield the number of new cases, deaths, and also the prevalence of disease. They explicitly represent disease transmission and so introduce a dependence between the number of new cases in different years. These models involve parameters evidenced from previous epidemiological work, but must be calibrated to learn from data on TB reports, deaths and prevalence. Calibration means adjusting imperfectly known model parameters in order to match observed model outputs to the data. This process provides a model that may be used to make predictions about burden, but may also teach us something about the underlying processes. Many of the parameters concerning the epidemiology and disease course of TB are quite uncertain, and this uncertainty is rarely represented fully in models needing calibration, but will be done in this project using statistical techniques that also allow comparison of different models' performance. TB burden estimation and calibration of transmission models are almost always carried out on a country-by-country basis. Many parameters describing disease progression are likely to be similar in different countries, even if their exact values differ for unknown reasons. Hierarchical modelling techniques allow such parameters to be correlated between countries. This can improve precision, particularly for countries with little data, as estimates can be informed by data from neighbouring countries. I will explore these techniques for the transmission model, and also in statistical modelling aiming to account for the observed patterns of drug-resistance. The transmission model will ultimately be extended to include different types of drug resistance. As new treatments and vaccines emerge, those with responsibility for public health will want to understand the potential impact these new technologies can have in terms of gains in health, and changes in spending. Producing cost-effectiveness and budget impact evidence requires a model that includes transmission, in order to account for indirect benefits accrued by avoiding secondary cases. We will use our model to provide guidance to decision-makers seeking to maximise health gain with limited resources. We will also analyse sources of uncertainty in the model to identify future research that would have most value in increasing the precision of burden estimates and in reducing decision uncertainty around the introduction of new interventions.","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 SHEFFIELD"], "activity_status_code":"4", "activity_date_iso_date":["2017-07-01T00:00:00Z","2017-09-01T00:00:00Z","2022-06-30T00:00:00Z","2022-08-31T00:00:00Z"], "activity_date_type":["1","2","3","4"], "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"], 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Astronomy Global Network"], "description_narrative":["We propose to build partnerships between the three separate projects in development through radio astronomy that we have already established via the Newton Fund in Africa, Latin America and South East Asia. This collaboration will form a global network of expertise in the mobilization of radio astronomy for economic development. The network will establish and build 'south-south' connections that will help the sharing of experiences and lessons learned in how to translate the high tech skills of radio astronomy into local job creation and entrepreneurship. The activities in this project centre on four international workshops that each focus on a key aspect of economic development through radio astronomy research. These include the conversion of old telecommunications dishes into radio telescopes, the formation of regional collaborations using networks of radio telescopes working together, utilizing the big data aspects of radio astronomy for translation into other areas of industry and commerce, and the transfer of the high tech skills in radio astronomy into the related areas of space science, geodesy, satellite communications and telecommunications and entrepreneurship. We will encourage other low- and middle-income countries (LMICs) in the three continental regions to join the established activities and build strong regional collaborations around this theme. This will help cement the UK's position as a world leader in radio astronomy and its applications.","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-GOV-STFC-12345","GB-GOV-STFC-12345","GB-COH-RC000658"], "participating_org_role":["1","2","3","4"], "participating_org_type":["10","15","15","80"], "participating_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY","SCIENCE AND TECHNOLOGY FACILITIES COUNCIL","SCIENCE AND TECHNOLOGY FACILITIES COUNCIL","UNIVERSITY OF LEEDS"], "activity_status_code":"4", "activity_date_iso_date":["2018-01-01T00:00:00Z","2018-01-01T00:00:00Z","2019-12-31T00:00:00Z","2019-12-31T00:00:00Z"], "activity_date_type":["1","2","3","4"], "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"], "activity_scope_code":"3", "recipient_country_code":["BF","MG","KE","ID"], "recipient_country_percentage":[25.0,25.0,25.0,25.0], "sector_code":["11430"], "sector_vocabulary":["1"], "policy_marker_code":["1","5","6","7","8","10","11","12"], "policy_marker_significance":["0","0","0","0","0","0","0","0"], "policy_marker_vocabulary":["1","1","1","1","1","1","1","1"], "collaboration_type_code":"1", "default_flow_type_code":"10", "default_finance_type_code":"110", "default_aid_type_code":["D02"], "default_tied_status_code":"5", "budget_status":["1","1","1"], "budget_type":["1","1","1"], "budget_period_start_iso_date":["2017-04-01T00:00:00Z","2018-04-01T00:00:00Z","2019-04-01T00:00:00Z"], "budget_period_end_iso_date":["2018-03-31T00:00:00Z","2019-03-31T00:00:00Z","2020-03-31T00:00:00Z"], "budget_value":[42938.15,172100.4,129857.99], "budget_value_currency":["GBP","GBP","GBP"], "capital_spend_percentage":0.0, "transaction_type":["3","3","3","3","3","3","3","3","3","2"], "transaction_date_iso_date":["2020-06-30T00:00:00Z","2019-12-31T00:00:00Z","2019-09-30T00:00:00Z","2019-06-30T00:00:00Z","2019-03-31T00:00:00Z","2018-12-31T00:00:00Z","2018-09-30T00:00:00Z","2018-06-30T00:00:00Z","2018-03-31T00:00:00Z","2018-01-01T00:00:00Z"], "transaction_value":[-15266.75,43286.09,43285.95,43285.95,43285.95,42938.15,42938.15,42938.15,42938.15,344896.54], "transaction_value_currency":["GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP"], "transaction_value_date":["2020-06-30T00:00:00Z","2019-12-31T00:00:00Z","2019-09-30T00:00:00Z","2019-06-30T00:00:00Z","2019-03-31T00:00:00Z","2018-12-31T00:00:00Z","2018-09-30T00:00:00Z","2018-06-30T00:00:00Z","2018-03-31T00:00:00Z","2018-01-01T00:00:00Z"], "hierarchy":1, "transaction_value_usd":[-19116.62247191978,56834.4957998265,53505.69337234231,54872.83755931313,57007.814845652734,54431.69767301002,56084.262436904326,57070.517564307745,59984.94361579121,476344.72612369026] },{ "default_currency":"GBP", "default_lang":"en", "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_S019170_1", "reporting_org_ref":"GB-GOV-13", "reporting_org_type_code":"10", "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"], "title_narrative":["MICA: Development of new agents for the treatment of cryptosporidiosis"], "description_narrative":["A recent clinical study in Africa and South Asia has found that cryptosporidiosis is one of the most significant causes of death and illness from diarrheal diseases amongst children in the developing world. Cryptosporidiosis is caused by a single-celled protozoan parasite; the predominant species infecting humans are called Cryptosporidium hominis and Cryptosporidium parvum. This parasite mainly lives in the cells in the gut wall and has a complex life-cycle. Infection occurs due to consumption of water or food contaminated with the parasites. Parasites are spread from an infected individual through their faeces. In people who are healthy and well nourished, the disease clears naturally within a couple of weeks. However, in people who are malnourished (particularly in young children) and people with an immune system that is not functioning properly (for example HIV/AIDS victims), the disease can have a much more significant impact. It is the major contributor to life-threatening diarrhea in young children, with 2.9-4.7 million cases in children under 24 months in sub-Saharan Africa and the Indian sub-continent, leading to more than 200,000 deaths per year. Cryptosporidiosis is also associated with malnutrition and stunted growth in children and probably causes chronic infections, which last for weeks or months. The only drug registered for the treatment of this disease is nitazoxanide, which is not very effective, especially in those patients who are most severely affected due to a weak immune system and/ or malnutrition. Therefore there is an urgent need for the development of new drugs to treat: (1) children <24 months, especially those that are malnourished and with chronic diarrhea; and (2) immunocompromised children and adults with advanced AIDS and chronic diarrhea. Cryptosporidium may be the cause of as much as 75% of chronic diarrhea in this patient cohort. We have discovered some chemical starting points that can be used for a drug discovery programme. We have a series of compounds that kill the parasites and also are very effective in clearing the parasites from rodent models of cryptosporidiosis. The compounds are thought to work through preventing the parasite making proteins. The aim of this project is to take these starting points and optimise them to make a molecule which has the potential to be a drug. This will require us to optimise multiple features of the molecule: its ability to kill the parasite, its ability to reach the sites in the body where the parasite resides without being broken down, and its safety. At the end of this project we hope to have a \"preclinical candidate\". This is a compound that we think should be suitable to enter human clinical trials. The steps after this project, prior to human clinical trials will be to make the compound on a larger scale under properly defined conditions and to carry out formal safety testing.","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-SC-015096"], "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 DUNDEE"], "activity_status_code":"4", "activity_date_iso_date":["2018-12-01T00:00:00Z","2019-05-01T00:00:00Z","2021-07-31T00:00:00Z","2023-01-31T00:00:00Z"], "activity_date_type":["1","2","3","4"], "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"], "activity_scope_code":"2", "recipient_country_code":["BI","KM","ET","KE","MG","MW","MU","MZ","ZW","RW","ER","SO","DJ","SD","SS","TZ","UG","ZM","AO","CM","CF","TD","CG","CD","GA","GQ","ST","ZA","BW","LS","NA","SZ","CV","BJ","GM","GH","GN","GW","CI","LR","ML","MR","NE","NG","SN","SL","SH","TG","BF"], "recipient_country_percentage":[2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123,2.0408163265306123], "sector_code":["12182"], "sector_vocabulary":["1"], "policy_marker_code":["1","5","6","7","8","10","11","12"], "policy_marker_significance":["0","0","0","0","0","0","0","2"], "policy_marker_vocabulary":["1","1","1","1","1","1","1","1"], "collaboration_type_code":"1", "default_flow_type_code":"10", "default_finance_type_code":"110", "default_aid_type_code":["D02"], "default_tied_status_code":"5", "budget_status":["1","1"], "budget_type":["1","1"], "budget_period_start_iso_date":["2019-04-01T00:00:00Z","2020-04-01T00:00:00Z"], "budget_period_end_iso_date":["2020-03-31T00:00:00Z","2021-03-31T00:00:00Z"], "budget_value":[943848.8,885292.5], "budget_value_currency":["GBP","GBP"], "capital_spend_percentage":0.0, "transaction_type":["3","3","3","3","3","3","3","3","2"], "transaction_date_iso_date":["2021-03-31T00:00:00Z","2020-12-31T00:00:00Z","2020-09-30T00:00:00Z","2020-06-30T00:00:00Z","2020-03-31T00:00:00Z","2019-12-31T00:00:00Z","2019-09-30T00:00:00Z","2019-06-30T00:00:00Z","2018-12-01T00:00:00Z"], "transaction_value":[179651.53,229893.98,237873.51,237873.53,235962.24,235962.24,235962.24,235962.24,2165959.19], "transaction_value_currency":["GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP"], "transaction_value_date":["2021-03-31T00:00:00Z","2020-12-31T00:00:00Z","2020-09-30T00:00:00Z","2020-06-30T00:00:00Z","2020-03-31T00:00:00Z","2019-12-31T00:00:00Z","2019-09-30T00:00:00Z","2019-06-30T00:00:00Z","2018-12-01T00:00:00Z"], "hierarchy":1, "transaction_value_usd":[248939.80718950738,307480.5939836779,308177.97882575076,297858.9725431336,292014.99550130573,309817.65593052306,291672.5464242103,299125.1818581239,2745736.269544861] },{ "default_currency":"GBP", "default_lang":"en", "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_N023005_1", "reporting_org_ref":"GB-GOV-13", "reporting_org_type_code":"10", "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"], "title_narrative":["Rational Design, Synthesis and Biological Evaluation of Benzimidazoles; Towards a Novel Therapy Selectively Targeting C. neoformans beta-tubulin"], "description_narrative":["The Need: Cryptococcus neoformans (C. neoformans) is a yeast like fungus which manifests as meningitis and less frequently pneumonia within the human body. In sub-Saharan Africa C. neoformans causes more deaths annually than tuberculosis. C. neoformans is the most common cause of fungal infection in patients with AIDS and there are an estimated 1 million cases of cryptococcal meningitis worldwide each year. The current drugs used to treat this disease are a 2 week course of amphotericin B and 5-flucytosine followed by a long term course of fluconazole. Amphotericin B and 5-flucytosine are associated with toxicity and fluconazole suppresses the growth of the fungus but does not completely remove it from the body. There is a therefore a great need for new drugs to treat C. neoformans infections. These drugs must have less toxicity and work better against the disease. The aim of this proposal is to complete the early stage drug discovery activities required to ultimately develop new drugs for cryptococcal meningoencephalitis that can be used in sub-Saharan Africa. The Concept: It has previously been reported within scientific papers that a class of compound called the benzimidazoles (widely used to treat worm infections in humans and as fungicides in agriculture) have good activity against C. neoformans in a laboratory and this has subsequently been confirmed by work here at the University of Liverpool (UoL). Benzimidazoles have been shown to interfere with cell division in C. neoformans through binding to beta-tubulin. Beta-tubulin is a protein that is essential for cell division and growth, when benzimidazoles bind to beta-tubulin the fungal cell can no longer grow. More recently, unpublished studies carried out at UoL have shown flubendazole to be active against C. neoformans in the mouse model. Humans also have beta-tubulin so it is essential that any new drug developed against the beta-tubulin target is selective for C. neoformans beta-tubulin. Medicinal chemistry (modification of the chemical structure of a drug) can be used to improve both selectivity for beta-tubulin and activity against C. neoformans. The Solution: Identification of an active class of compound, against a known target, with established whole cell C. neoformans and animal model activity provides an excellent starting point for medicinal chemistry modification. To date benzimidazole compounds have never undergone medicinal chemistry optimisation to establish beta-tubulin selectivity or to improve C. neoformans activity. The two most commonly use benzimidazole drugs (Flubendazole and albendazole) are extensively metabolised within the body and have a limited ability to move from the stomach into the blood stream. New compounds will be designed using information from computer models to predict how they are likely to behave within the body. In order to improve the safety profile of the newly designed compounds their selectivity for C. neoformans beta-tubulin over human beta-tubulin will be measured in the laboratory (alongside activity against C. neoformans) and computer models of the binding sites of the two tubulins used to look at how new compounds are likely to bind better with C. neoformans beta-tubulin. Once C. neoformans activity, selectivity for beta-tubulin and improved levels of circulating drug have been established the compounds will move into a mouse model of C. neoformans infection. Impact: The long term aim is to develop a single therapy that does not require subsequent long term treatment with fluconazole and that can be given both orally and by injection. Given the number of patients affected by C. neoformans this project has the potential to have a dramatic beneficial impact on individuals and societies. Development: Compounds demonstrating activity in the mouse model will form the basis of further funding applications to progress the new drugs through the drug development pipeline.","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-RC000660"], "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 LIVERPOOL"], "activity_status_code":"4", "activity_date_iso_date":["2016-05-01T00:00:00Z","2016-07-01T00:00:00Z","2019-04-30T00:00:00Z","2019-12-31T00:00:00Z"], "activity_date_type":["1","2","3","4"], "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"], "activity_scope_code":"2", "recipient_country_code":["BF","MW","UG","ZM"], "recipient_country_percentage":[25.0,25.0,25.0,25.0], "sector_code":["12182"], "sector_vocabulary":["1"], "policy_marker_code":["1","5","6","7","8","10","11","12"], "policy_marker_significance":["0","0","0","0","0","0","0","0"], "policy_marker_vocabulary":["1","1","1","1","1","1","1","1"], "collaboration_type_code":"1", "default_flow_type_code":"10", "default_finance_type_code":"110", "default_aid_type_code":["D02"], "default_tied_status_code":"5", "budget_status":["1","1","1"], "budget_type":["1","1","1"], "budget_period_start_iso_date":["2016-04-01T00:00:00Z","2017-04-01T00:00:00Z","2018-04-01T00:00:00Z"], "budget_period_end_iso_date":["2017-03-31T00:00:00Z","2018-03-31T00:00:00Z","2019-03-31T00:00:00Z"], "budget_value":[102914.06,143800.8,143175.43], "budget_value_currency":["GBP","GBP","GBP"], "capital_spend_percentage":0.0, "transaction_type":["3","3","3","3","3","3","3","3","3","3","3","3","2"], "transaction_date_iso_date":["2020-06-30T00:00:00Z","2019-03-31T00:00:00Z","2018-12-31T00:00:00Z","2018-09-30T00:00:00Z","2018-06-30T00:00:00Z","2018-03-31T00:00:00Z","2017-12-31T00:00:00Z","2017-09-30T00:00:00Z","2017-06-30T00:00:00Z","2017-03-31T00:00:00Z","2016-12-31T00:00:00Z","2016-09-30T00:00:00Z","2016-05-01T00:00:00Z"], "transaction_value":[26851.59,35628.54,35628.54,35628.54,36289.81,36289.83,36289.83,36289.83,34931.31,34931.32,33991.37,33991.37,425518.97], "transaction_value_currency":["GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP","GBP"], "transaction_value_date":["2020-06-30T00:00:00Z","2019-03-31T00:00:00Z","2018-12-31T00:00:00Z","2018-09-30T00:00:00Z","2018-06-30T00:00:00Z","2018-03-31T00:00:00Z","2017-12-31T00:00:00Z","2017-09-30T00:00:00Z","2017-06-30T00:00:00Z","2017-03-31T00:00:00Z","2016-12-31T00:00:00Z","2016-09-30T00:00:00Z","2016-05-01T00:00:00Z"], "hierarchy":1, "transaction_value_usd":[33622.854163510674,46922.967187757975,45165.47447458133,46536.71356599536,48233.98863272849,50697.18668309297,48643.785561317636,48367.33905228542,44717.91207631076,43082.234854237635,42476.03963681046,44665.94716450353,618309.1524781471] },{ "default_currency":"GBP", "default_lang":"en", "iati_identifier":"GB-GOV-13-FUND--GCRF-MR_R015600_1", "reporting_org_ref":"GB-GOV-13", "reporting_org_type_code":"10", "reporting_org_narrative":["DEPARTMENT FOR BUSINESS, ENERGY & INDUSTRIAL STRATEGY"], "title_narrative":["MRC Centre for Global Infectious Disease Analysis"], "description_narrative":["The continuing threat from new infectious diseases has been highlighted in recent years by the emergence of MERS-coronavirus in the Middle East, Ebola in West Africa and Zika in Latin America. Preparing for and responding to such threats is a priority for public health agencies and governments worldwide. Equally importantly, as scientific research delivers new approaches to controlling existing infectious diseases such as malaria, HIV, tuberculosis and polio, there is a need to determine what interventions are likely to work best to limit the disease and illness caused by a specific disease in a particular setting. In this context, computer modelling of the spread of diseases in populations coupled with scientifically rigorous data analysis have proven themselves as powerful tools for giving insight into how diseases spread and what can be done to limit that control that spread. The Centre for Global Infectious Disease Analysis undertakes research on these scientific methods and applies them to disease threats of concern. A key feature of the Centre is the close links it has made with with public health agencies - such as the Public Health England, the Centers for Disease Control and Prevention in the US (CDC), and the World Health Organization (WHO) - organisations which have to formulate and implement strategies to control infectious diseases. Senior scientists in the Centre are world-leaders in infectious disease modelling and analysis. They have broad experience in responding to real epidemics, and undertaking epidemiological research on endemic diseases (such as malaria, HIV, tuberculosis and polio). Their work directly influences disease control policy through the many interactions the Centre has with public health organisations and governments. Funding provided by MRC and Imperial College has allowed dedicated investment into the development of close collaborative partnerships with PHE, CDC and WHO and governments and research centres in many low and middle income countries (LMICs). We also work closely with other important organisations who work on improving health in LMICs (notably the Bill and Melinda Gates Foundation, The Global Fund and Gavi). With each, our collaborative research has both scientific interest to Centre researchers and contributes to the evidence base for public health decisions. Centre funding supports a core technical capacity available to all projects and pays for dedicated liaison staff who facilitate and enhance our partnerships with major global health organisations and LMICs. MRC funding has also facilitated a greater focus on collaboration, training and career development within the Centre - training the next generation of quantitative infectious disease epidemiologists. We are also involved in increasing knowledge of advanced modelling methods in public health institutions and the wider infectious disease research community, and so have run a large number of introductory short-courses and workshops (in 13 countries in the last 5 years) This applied activity depends on more fundamental research undertaken in the Centre on the transmission dynamics of different diseases, how diseases evolve genetically over time, and on analysing new approaches to control or treat diseases. This research is interdisciplinary, with Centre researchers working with leading clinical and experimental scientists around the world. Continued Centre funding will allow existing partnerships to be sustained and enhanced, and new collaborations with researchers and health agencies in LMICs to be developed. By supporting PhD training and postdoctoral career development, it will also continue to expand the UK skill base in mathematical modelling and advanced analysis applied to health problems. Last, continued MRC support will pump-prime new priority research areas, including work on improving the development of new vaccines and on tackling the global challenge posed by antimicrobial resistance.","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. 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Nearly half a million people died from the disease in 2015, the majority of deaths being in children under the age of five. The malaria parasite is spread by infected mosquitoes and the most effective way to monitor the disease is to monitor populations of these mosquitoes. However, current tools for sampling malarial mosquitoes are time-consuming and labour intensive, making them expensive and difficult to standardize. Accordingly, data between countries and regions cannot be reliably compared. To solve this problem, we have developed a mosquito trap that exploits the blood-seeking behaviour of mosquitoes by mimicking the sensory stimuli that a mosquito follows when searching for a person to bite. These include the look, smell and temperature of warm-blooded hosts. We have incorporated these stimuli into a trap that lures mosquitoes towards it and then captures them when they land. Our project will test this \"Human Decoy\" Trap against current methods used in mosquito monitoring to determine whether the Human Decoy Trap can overcome the limitations of existing tools. We will evaluate if Human Decoy Trap catches are suitably similar to those of current traps in terms of numbers of mosquitoes and other important data related to malaria that can be extracted from mosquitoes caught by traps, such as the proportion of caught mosquitoes infected with malaria parasites. Over 90 countries, mostly low and middle income, are malaria-endemic. We will work in Burkina Faso, Benin and Cameroon, three West African countries where malaria causes thousands of deaths every year, but differing in intensity and seasonality of transmission and with different mosquito species involved. This will help us to understand whether there are differences in trap performance in a wide range of malaria settings. In addition, we will work with end-users of the trap, namely local communities, public health operatives and field technicians, to better understand their perspectives and needs regarding mosquito sampling and control. During the course of the project, we will use data we collect to optimize and improve the trap's performance and design. This will help us to develop a commercial prototype that is effective and acceptable to end-users, maximising the likelihood the trap will be adopted into the communities and sectors that need it the most. Longer-term, we envision a version of the Human Decoy Trap that can be deployed as a mosquito control tool. The most effective way of controlling malaria is to reduce the number of infective mosquito bites a person receives. This is currently achieved by providing people with insecticide-treated bed nets to protect them from bites whilst they sleep and spraying the walls inside houses thus killing mosquitoes that rest there. However, neither of these options protects people from mosquitoes that may bite them outdoors during the day or just before they go to bed at night. Data from this current project will be used to provide preliminary evidence for the suitability of the Human Decoy Trap as a control tool that is specifically targeted at malaria mosquitoes biting outdoors, which may also be effective against other species of mosquitoes that can carry other infectious diseases, such as dengue fever, chikungunya and Zika viruses. Such an improved sampling method would enhance the quality of data necessary for efficient targeting and evaluation of malaria control intervention activities and reduce the cost of collecting it. A successful outdoor mosquito control device would help to reduce the population of infected mosquitoes that cause malaria. Ultimately, the combined effect of these tools would be a reduction in the human suffering and death caused by malaria to millions of people every year and an improvement in the social and economic prospects of the 3.2 billion people living at risk of malaria.","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. 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