Project description DEENESFRITPL Gametocytes as a reservoir of the malaria parasites in human hosts The malaria parasite gametocytes are the precursors of male and female gametes in the human host, formed through the developmental switch from asexual replication in erythrocytes. Gametocytes differentiate into male and female gametes in mosquito’s midgut, and after complete sexual reproduction, mature sporozoites accumulate in the vector's salivary gland, ready to be inoculated into a new host. Many individuals in the endemic areas harbour low but transmissible gametocyte densities. The EU-funded QUANTUM project will significantly improve understanding of the production and infectivity of gametocytes and the epidemiological impact of human immune responses. The work in different selected settings in Africa will provide a major advancement in understanding the human infectious reservoir for malaria and will have direct implications for disease elimination. Show the project objective Hide the project objective Objective Background: A major challenge for malaria elimination is its phenomenally efficient spread through sexual stage parasites (gametocytes). Many individuals in endemic settings harbour low but transmissible gametocyte densities. It is currently unclear how gametocyte density translates into the likelihood that an infected mosquito gives rise to secondary infections, who drive malaria transmission at population level and how anti-gametocyte immunity affects gametocyte production and infectivity. I hypothesize that secondary infections can arise from low-density infections but that higher gametocyte densities result in comparatively more infectious mosquitoes and an increased number of secondary infections. I further hypothesize that malaria transmission efficiency and changes therein can only be accurately predicted if anti-gametocyte immunity is thoroughly understood and that the rapid loss of gametocyte immunity during effective control results in increased transmission efficiency.Aims and approach: I will perform the first-ever direct assessment of numbers of malaria parasites ejected by mosquitoes in relation to natural gametocyte densities. Using novel genotyping approaches, longitudinal sampling of infections at unsurpassed resolution and state-of-the art analytical approaches, I will perform the most comprehensive molecular evaluation of malaria transmission in a real community ever performed. Lastly, I will quantify the impact of immune responses that reduce gametocyte density and infectivity by novel immune-profiling approaches and mathematical transmission models.Importance and innovation: this project will profoundly improve understanding of the production and infectivity of gametocytes and the epidemiological impact of human immune responses that influence these processes. The work in different African settings will provide a major leap forward in understanding the human infectious reservoir for malaria and has direct implications for elimination Fields of science medical and health scienceshealth sciencesinfectious diseasesmalariamedical and health sciencesbasic medicineimmunologynatural sciencesbiological scienceszoologyinvertebrate zoology Keywords malaria gametocyte epidemiology transmission immuno-epidemiology Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2019-COG - ERC Consolidator Grant Call for proposal ERC-2019-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM Net EU contribution € 1 851 250,00 Address Geert grooteplein 10 zuid 6525 GA Nijmegen Netherlands See on map Region Oost-Nederland Gelderland Arnhem/Nijmegen Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (3) Sort alphabetically Sort by Net EU contribution Expand all Collapse all STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM Netherlands Net EU contribution € 1 851 250,00 Address Geert grooteplein 10 zuid 6525 GA Nijmegen See on map Region Oost-Nederland Gelderland Arnhem/Nijmegen Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 THE REGENTS OF THE UNIVERSITY OF CALIFORNIA United States Net EU contribution € 148 750,00 Address Franklin street 1111 12 floor 94607 Oakland ca See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 STICHTING RADBOUD UNIVERSITEIT Participation ended Netherlands Net EU contribution € 0,00 Address Houtlaan 4 6525 XZ Nijmegen See on map Region Oost-Nederland Gelderland Arnhem/Nijmegen Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
