Quantum: Quantifying the spread of P. falciparum malaria

Investigator: Bryan Greenhouse, MD

Location(s): Gambia


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. "Understanding who sustains pathogen transmission is important for all infectious diseases. For COVID-19, information on the importance of non-symptomatic individuals in spreading the virus is important for public health measures. This is the same for the malaria parasite. The QUANTUM project will quantify who is responsible for malaria transmission (for giving rise to secondary infections. In the laboratories in Burkina Faso and Uganda, we will examine what makes an infectious mosquito by examining how many malaria parasites are injected by malaria-infected mosquitoes. This will be related to characteristics of the human donor who infected the mosquito (e.g. was this a clinical case or an asymptomatic malaria-infected individual). In The Gambia, we will examine transmission networks in villages where malaria is endemic. We will aim to quantify the number of secondary infections arising from different human populations. Lastly, we will examine the impact of human anti-gametocyte immunity on malaria transmission and gametocyte production. Together, these data will help inform malaria control programs on what populations need to be prioritized for malaria interventions for maximum impact. In addition, the project will inform on the utility and potency of natural and vaccine-induced anti-gametocyte immunity in curbing malaria transmission. Since the start of the project, experiments to help understand what makes an infectious mosquito have been performed using cultured malaria parasites and artificial skin tissue. This work will now be moved to field-settings.
In The Gambia, villages have been selected for transmission network studies. Blood collection procedures were optimized to allow detailed genotyping from low parasite-density samples. Upcoming work will utilize this methodology to examine the genetic relatedness between infections as they appear in space and time.
To better understand gametocyte immunity, we optimized an assay to quantify recognition of activated malaria transmission stages (gametes) that is now utilized on archived samples to better understand the kinetics and functionality of anti-gametocyte immunity."