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Quantifying the spread of P. falciparum malaria

Periodic Reporting for period 2 - QUANTUM (Quantifying the spread of P. falciparum malaria)

Reporting period: 2022-01-01 to 2023-06-30

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.
Experiments to help understand what makes an infectious mosquito have been performed using cultured malaria parasites and blood donated by naturally infected parasite carriers. With a newly developed pipeline, we measure malaria parasites during their development in mosquitoes, up to the point they are injected by the mosquito inartificial skin tissue. We are directly comparing high- and low- infected mosquitoes in terms of their parasite development and transmission potential.

In The Gambia, villages have participated in repeated sampling for transmission network studies. Blood collection procedures were optimized to allow detailed genotyping from low parasite-density samples. Inhabitants of three villages in the Upper River Region of this country donated blood samples repeatedly 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 has been utilized on samples from Uganda to better understand the kinetics and functionality of anti-gametocyte immunity. This work includes the largest-ever effort to characterize functional transmission blocking immunity in naturally exposed individuals.
A mosquito taking a blood from a malaria-infected study participant