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CORDIS

Quantifying the spread of P. falciparum malaria

Project description

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.

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

Host institution

STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM
Net EU contribution
€ 1 851 250,00
Address
GEERT GROOTEPLEIN 10 ZUID
6525 GA Nijmegen
Netherlands

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Region
Oost-Nederland Gelderland Arnhem/Nijmegen
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 851 250,00

Beneficiaries (3)