Periodic Reporting for period 4 - QUANTUM (Quantifying the spread of P. falciparum malaria)
Période du rapport: 2025-01-01 au 2025-06-30
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.
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 measured malaria parasites during their development in mosquitoes, up to the point they are injected by the mosquito inartificial skin tissue. We uncovered that there is a previously unappreciated bottleneck for malaria parasites in mosquitoes and found evidence that i) a non-negligible proportion of infected mosquitoes does not inject parasites during probing; ii) mosquitoes with a high infection burden expell more parasites upon probing without the need to take a bloodmeal.
In Ethiopia, Uganda and The Gambia, we examined how malaria spreads through communities. We were able to detect transmission chains and uncovered that a novel mosquito vector plays an important role in spreading malaria in Ethiopia. This work has helped define a regional containment strategy for this invasive mosquito. In Uganda, we demonstrated in several cohorts that school age children are an important source of onward transmission of malaria parasites to mosquitoes. This work has supported a policy guideline to extend malaria interventions, including chemoprevention strategies, to this age group. This is expected to reduce the clinical burden in this age group and also have a beneficial community effect by reducing community-wide transmission.
In settings across Africa, we examined naturally acquired immunity to the transmission stages of malaria parasites. We uncovered that strong functional immunity that can prevent transmission to mosquitoes can be naturally acquired, is associated to recent exposure to malaria parasites and can be long-lived in a minority of individuals. This work identified a number of potent monoclonal antibodies that may be used as intervention or help improve vaccination strategies.
In Ethiopia, Uganda and The Gambia, we examined how malaria spreads through communities. We were able to detect transmission chains and uncovered that a novel mosquito vector plays an important role in spreading malaria in Ethiopia. This work has helped define a regional containment strategy for this invasive mosquito. In Uganda, we demonstrated in several cohorts that school age children are an important source of onward transmission of malaria parasites to mosquitoes. This work has supported a policy guideline to extend malaria interventions, including chemoprevention strategies, to this age group. This is expected to reduce the clinical burden in this age group and also have a beneficial community effect by reducing community-wide transmission.
In settings across Africa, we examined naturally acquired immunity to the transmission stages of malaria parasites. We uncovered that strong functional immunity that can prevent transmission to mosquitoes can be naturally acquired, is associated to recent exposure to malaria parasites and can be long-lived in a minority of individuals. This work identified a number of potent monoclonal antibodies that may be used as intervention or help improve vaccination strategies.
The work in this project has challenged the dogma that all infected mosquitoes are equally infectious and quantified developmental bottlenecks of malaria parasites in mosquitoes.
In addition, the work has described for the first time the natural acquisition and loss of (functional) immune responses to the transmission stages of malaria parasites. This helps better understand the infectious reservoir for malaria and forms a starting point to use these insights to improve malaria and develop novel immunologicals.
In addition, the work has described for the first time the natural acquisition and loss of (functional) immune responses to the transmission stages of malaria parasites. This helps better understand the infectious reservoir for malaria and forms a starting point to use these insights to improve malaria and develop novel immunologicals.