Population genomics of Plasmodium malariae in Southern Nigeria
Plasmodium malariae was first described as infectious to humans over a century ago yet not much is known about the role it plays in malaria transmission. The parasite species is widespread throughout endemic regions in sub-Saharan Africa, occurring mostly as mixed infections with Plasmodium falciparum. The emergence of artemisinin resistant P. falciparum parasites in Southeast Asia, makes it important to assess the impact of antimalarial drugs on the Plasmodium species prevalent in sub-Saharan Africa. This study employs whole genome sequencing to determine if selection by antimalarial drugs, the human and vector hosts has resulted into similar genetic signatures across the genome. Markers identified could be integrated into antimalarial resistance surveillance that is a key component of elimination programs. The Project is in collaboration with the Nigerian Institute of Medical Research (NIMR), Lagos and the University of Calabar Teaching Hospital, Nigeria. It is sponsored by a Postdoctoral Fellowship from the Wellcome Trust DELTAS-Africa initiative - Developing Excellence in Leadership and Genetic Training for Malaria Elimination in sub-Saharan Africa (DELGEME), Bamako, Mali.

The Gambia Hepatitis Intervention Study (GHIS)
The Gambia Hepatitis Intervention Study (GHIS) is a long-standing collaborative project between the world health organization’s international agency for research on cancer (WHO-IARC), MRC and The Gambia Government, set up in 1986.The project is funded by WHO-IARC and was responsible for the introduction of infant Hepatitis B immunization to The Gambia. Between 1986 and 1990 the phased introduction of Hepatitis B virus (HBV) vaccination to all Gambian children as part of the Expanded Programme of Immunization (EPI), allowed the recruitment of two groups of infants of just over 60,000 each who either received or did not receive HBV vaccine at birth.

Mass drug administration of ivermectin and dihydroartemisinin-piperaquine as an additional intervention for malaria elimination (MASSIV)
This is a community-based cluster-randomized trial in which a novel approach to interrupt residual malaria transmission will be tested. This trial aims at establishing whether by mass drug administration (MDA) with ivermectin (IVM) combined with dihydroartemisinin-piperaquine (DP) can reduce or interrupt malaria transmission in medium to low transmission settings by reducing vector survival and the human reservoir of infection. MDA with IVM and DP will be implemented in 16 intervention villages and 16 control villages will receive standard malaria control interventions as implemented by the National Malaria Control Program. The primary outcomes will be the prevalence of malaria infection and the vector’s parous rate.

Will the ongoing use of a two-dose, rather than three-dose schedule of pneumococcal conjugate vaccine, have similar impact in rural Gambia? (PVS - JGHT)
The Pneumococcal Vaccine Schedules study (PVS) aims to test whether an alternative schedule for pneumococcal conjugate vaccine, using one early dose and one later booster dose will have the same impact as the standard schedule of three early doses. PVS will be based in rural Gambia around Basse and Bansang and enroll approximately 40,000 infants over 4 years. PVS is a collaborative study with the Gambian Ministry of Health. The study will provide evidence required by WHO to review their recommendations for the scheduling of PCV.

The Rotavirus vaccine effectiveness study (VIDA)
VIDA (Vaccine Impact on Diarrhoea in Africa) is a 3-year case control study taking place in The Gambia, Mali and Kenya to assess the incidence, etiology and clinical consequences of moderate-to-severe diarrheal disease among children aged <5 years following rotavirus vaccine introduction. VIDA study started in 2015 and successfully completed 3-years of enrolment. Data cleaning, data analysis and manuscript writing will continue for next 2 years.

Can improved housing provide additional protection against clinical malaria over current best practice? A household-randomised controlled trial
The primary objective is to assess whether improved housing reduces further the burden of clinical malaria where coverage of Long-Lasting Insecticidal nets LLIN is high. Approximately 800 children, boys and girls, aged 6 months – 13 years old resident in 800 households in the Upper River Region were recruited into a study cohort to assess the impact of the intervention on malaria.

Randomised controlled trial of early kangaroo mother care for hospitalised neonates <2000g (eKMC- Helen Brotherton's Fellowship)
Kangaroo mother care (KMC), consisting of prolonged, continuous skin-to-skin contact, reduces death and infections in stable preterm/LBW neonates, but benefits for unstable babies are not known. Using continuous KMC early in unstable neonates has a physiological basis, is a feasible and acceptable intervention and has been highlighted as a research priority to reduce preterm and neonatal mortality and improve morbidity.

Personalised Risk assessment in febrile illness to Optimise Real-life Management across the European Union (PERFORM)
The ‘Personalised Risk Assessment in Febrile Illness to Optimise Real-Life Management’ (PERFORM) project aims to improve the diagnosis and management of febrile children across Europe and Africa. The Gambia is the only site in Africa. The study is recruiting children between 1 month and 18 years at the Kanifing General Hospital and the Clinical Service Department, MRCG @ LSHTM. Seventy five percent of the 500 children targeted have been recruited as of July 2018.

Maximising the public health impact of interventions to control malaria in pregnancy through the translation of EDCTP-funded evidence-based global policies to country level policies and plans (IMPPACT)
The overall Objective is to ensure the translation of the WHO recommendations on the control of malaria in pregnancy into country policies and implementation plans. Specific aims are to develop and make widely-available a package of methodological tools defining optimal, cost-effective malaria in pregnancy interventions, to facilitate optimal uptake of evidence-based interventions for the control of malaria in pregnancy and to provide expertise to support national policy change and preparation for implementation. The project will directly support translation of WHO policy recommendations into country level policies and plans.

The relationship between malarial anaemia, neutrophil function and susceptibility to invasive bacterial disease (AMAN)
Bacteraemia in Africa has a fatality rate of ~20% and is predominantly due to Salmonella. Risk is associated with recent malaria infection rather than acute infection. Therefore, we hypothesize that chronic low-density (“asymptomatic”) malaria infections may lead to persistent neutrophil dysfunction. In the AMAN study, we investigate school-aged children with asymptomatic malaria infection and anaemia - describing their impact of neutrophil function and potential risk to bacterial sepsis.

A Phase 2 interventional, multicenter, randomized open-label study to determine the effective and tolerable dose of KAF156 and Lumefantrine Solid Dispersion Formulation in combination, given once daily for 1, 2 and 3-days to adults and children with uncomplicated Plasmodium falciparum malaria (CKAF)
CKAF (formally CKAF156A2202) is an early phase 2 randomised controlled trial of a new antimalarial in combination with a new formulation of lumefantrine compared to co-artem for the treatment of uncomplicated malaria. The study is a multi-centred trial sponsored by Novartis. Patients recruited to the study will be admitted to the ward at CSD for 3-4 days and then followed up for 42 days.

Reactive household self-administered treatment against residual malaria tranmission (RHOST)
The project aims to determine the impact of treating household contacts of clinical malaria cases with a full course of an antimalarial using the existing community health structures, on transmission. This inter-disciplinary study is being conducted in villages in the North-Bank-East and Lower-River Regions in The Gambia. Formative research into community perception and reaction to self-administered treatment was used to develop the intervention model. The primary outcome is the prevalence of malaria infection, determined by molecular methods with impact on health systems, costs and cost-effectiveness of the intervention also assessed.

Pre-delivery administration of azithromycin to prevent neonatal sepsis and death: a phase III double-blind randomized (Pregnanzi II)
Neonatal and maternal sepsis are major contributors to the high burden of mortality in sub-Saharan Africa (SSA). Simple interventions to reduce such burden are required. As the mother is an important source of infection for the newborn, an intervention able to decrease vertical transmission of pathogenic bacteria (mother to newborn) should substantially decrease neonatal mortality.

Rheumatic Heart Disease
The RHD Project is a 1-year pilot study (Jul.2017- Jul.2018) funded by the Wellcome Trust to generate baseline data on rheumatic heart disease (RHD) in The Gambia. The first phase (Nov-Dec2017) consisted of a hospital-based review of all registered RHD cases managed at the two main referral hospitals. The second phase (Jan-Jul2018) consisted of a population-based survey of children (5-19 years) and pregnant women to estimate the prevalence and related risk factors of RHD detected by echocardiography in these two high- risk groups.

Feasibility of the Nanobubble Technology for Detection of Malaria” (Malarisense 2)
The overall aim of this study were to evaluate the feasibility of the vapor nanobubble technology for malaria diagnostics, to optimize the procedure and the protocol of the transdermal and transmucosal diagnosis of the malaria with hemozoin-generated vapor nanobubbles by testing, to verify the optimized diagnostic procedures and the protocols of non-invasive transdermal/ transmucosal and minimally invasive diagnosis of malaria with the vapor nanobubbles and to determine the sensitivity and specificity of vapor nanobubble technology in diagnosing malaria in malaria suspected cases. , and to identify factors influencing the diagnostic accuracy of the technology.

Research towards infectious disease elimination on the Bijagós Archipelago of Guinea Bissau (West Africa)
The Bijagós islands in Guinea Bissau provide an ideal setting in which to study in detail the transmission dynamics and socio-behavioural determinants of infectious diseases, and to develop and evaluate new tools and strategies for their elimination. The Bissau-Guinean Ministry of Health has called for Neglected Tropical Disease (NTD) and malaria elimination as a priority. However, there are no recent good quality epidemiological data for the islands. The study is undertaking a detailed integrated mapping of NTDs and malaria and will gain insight into their patterns of transmission through socio-behavioural, epidemiological and vector studies.

The mechanisms underlying the production of natural mosquito repellents by human beings
Some human beings are bitten more than others by mosquitoes. From an evolutionary perspective this is fundamentally important since those that get bitten less often are less likely to die from lethal mosquito-borne diseases like malaria. Previous studies have shown that human differential attractiveness to mosquitoes is due to the natural production of key repellent chemicals given off by individuals who rarely get bitten. We hypothesise that differential repellency between individuals is mediated by genes that control the production of volatile repellents through the skin. Using a large cohort of identical and non-identical twins, we will investigate genes that control odours associated with attractiveness.

West African Network for TB AIDS and Malaria (WANETAM 2)
The West Africa network of excellence for clinical trials in TB, AIDS, and Malaria (WANETAM) proposes a renewed consortium, WANETAM-2, to build on the previous achievements in capacity building for clinical studies and interventions. The new network will structure training and collaboration through thematic nodes of excellence in TB, HIV/AIDS and Malaria and a new capacity strengthening in Neglected Tropical Diseases (NTD) and Ebola. The strategy of training and collaboration will focus on project-based training to build research leadership; hands-on clinical studies; resource and platform infrastructure development for data sharing and collaborative research; surveillance to build the evidence-base needed for designing clinical trials; diagnostics to support interventions; and building quality assurance management to support the steps for laboratory accreditation. There will be cross-cutting training to enhance professional development and scientific competency in clinical trials and research support. The work packages to support training activities, acquire capacity and foster stronger collaboration fall under 3 main areas, namely: 1. Surveillance; 2. Diagnostics; and 3. Clinical trial resources. The cross-cutting training includes Post-doctoral and Senior Clinical skills training and mentorship; MSc Online courses; Professional Development Courses; and Professional development internship.

African coaLition for Epidemic Research, Response and Training (ALERT)
ALERRT (African coaLition for Epidemic Research, Response and Training) combines the strengths of leading African and European partners in (Re-)emerging and Epidemic-Prone Infectious Diseases (REPID) clinical research, preparedness and response. It builds on efforts by the EDCTP Networks of Excellence WANETAM, CANTAM and EACCR, and internationally well-embedded research and training partners with extensive operational experience in outbreak preparedness and response, and the associated challenges in sub-Saharan Africa (SSA). The purpose of ALERRT is to reduce the public health and socio-economic impact of REPID in SSA. This will be achieved by building a sustainable clinical and laboratory research preparedness and response network, with the operational readiness to rapidly implement clinical and laboratory research in support of REPID control efforts at local, regional and international level.

Developing excellence in leadership, training and science (DELTAS) ‘Malaria Research Capacity Development in West and Central Africa’
This research and training programme will help to establish a critical mass of internationally-competitive scientists in West and Central Africa with a focus on malaria control and elimination. The scientists will deliver scientific evidence to support malaria elimination, where this is feasible, or to bring malaria control to the point where elimination may become achievable. These goals will be achieved by focusing on postdoctoral fellows and their progression to senior researchers/research leaders. PhD fellowships will be awarded competitively to promising young researchers, supervised by both the postdoctoral fellows and an established mentor from one of the participating institutions. The programme will build on the successful PhD and post-doctoral programmes carried out by the Malaria Capacity Development Consortium (MCDC), which supports this application.

Optimizing a deployable high efficacy malaria vaccine (OptiMalVax)
A highly effective malaria vaccine against Plasmodium falciparum should help prevent half a million deaths from malaria each year. New vaccine technologies and antigen discovery approaches now make accelerated design and development of a highly effective multi-antigen multi-stage subunit vaccine feasible. Leading malariologists, vaccine researchers and product developers will here collaborate in an exciting programme of antigen discovery science linked to rapid clinical development of new vaccine candidates. Our approach tackles the toughest problems in malaria vaccine design: choice of the best antigens, attaining high immunogenicity, avoiding polymorphic antigens and increasing the durability of vaccine immunogenicity and efficacy. We take advantage of several recent advances in vaccinology and adopt some very new technologies: sequencing malaria peptides eluted from the HLA molecules, parasites expressing multiple transgenes, multi-antigen virus-like particles constructed with new bonding technologies, delayed release microcapsules, and liver-targeted immunisation with vaccine vectors. We enhance our chances of success by using a multi-stage multi-antigen approach, by optimising the magnitude and durability of well-characterised immune responses to key antigens, and using stringent infectious challenges and functional assays as established criteria for progression at each stage.

Using medical-detection dogs to identify people with malaria parasites
The task of malaria elimination would be simpler if a non-invasive method was available for detecting infected individuals in populations where the parasite prevalence is low; infected individuals could then be treated with antimalarials. Dogs have a highly developed sense of smell and may be able to detect volatiles released from people carrying malaria parasites. This is a pilot study to determine whether trained dogs could detect malaria infections in Gambian children aged 5-13 years old. Samples of exhaled breath, skin odour and urine will be collected from 600 school children. Samples will be used to train medical-detection dogs in the UK. After two months of training a double-blinded study will be undertaken to assess the diagnostic accuracy of the dog. To assess the reaction of local people to medical-detection dogs, a well-disciplined dog with a ‘medical-detection dog’ coat will be introduced to residents of a Gambian village. Focus group discussions will assess the benefits and challenges of using medical-detection dogs for malaria surveillance in Gambian villages. If successful, this diagnostic approach could be used for mass screening of malaria cases in areas of low transmission.