Defining physiological correlates of the human malaria infectious reservoir

Malaria remains one of the leading causes of death worldwide and affects about half the global population, despite decades of public health efforts. The recent commitment to eliminate malaria by many endemic countries marks a shift in public health policy away from programs aimed at controlling disease burden towards one that emphasizes reducing transmission of the most virulent human malaria parasite, Plasmodium falciparum.

Only a very small fraction of malaria parasites within human blood are able to infect mosquitoes, however, these transmission stages have remained under-studied because they do not cause disease and are difficult to detect by conventional methods. Because malaria transmission stages are rarely detected, it has been assumed that only a small fraction of malaria-infected individuals are capable of infecting mosquitoes. Recent preliminary data suggest that this dogma is wrong and that people with low-density malaria infections can, in fact, transmit to mosquitoes very efficiently. In addition, it has been demonstrated that blood meals directly from the skin of an infected participant more commonly result in mosquito infection compared to blood meals from venous blood samples.

This led to the hypothesis that transmissible malaria parasite stages cluster under the skin where mosquitoes can find them most effectively. If this hypothesis is correct, all previous analyses of infectiousness based on venous blood are not accurate. The clustering of transmission stages under the skin may contribute considerably to the phenomenally efficient spread of malaria parasites in populations.

Together, this interdisciplinary study will test long-standing and powerful hypothesis using modern tools. As such it will lay the foundation for accurate predictions of malaria transmissibility at a population level that can inform public health interventions and timelines to achieve malaria elimination. If gametocytes are observed to cluster under the skin, this study will form the starting point for systematic mechanistic studies and may lead to novel transmission- blocking interventions.

Eliminating malaria will require a shift towards control policies that reduce transmission of the malaria parasite in addition to controlling disease, but progress in the design of these policies is currently limited by our poor understanding of human infectiousness. Here a series of molecular and histological tools will be combined with experimental feeding assays to measure infectiousness parameters in human and mosquito. Together, these studies will address one of the most urgent problems in malaria epidemiology: how to define the human infectious reservoir.

Defining physiological correlates of the human malaria infectious reservoir

Asymptomatic Reservoir
Measurement of Transmission

Feb 2016 — Jan 2018

$413,545

Burkina Faso
Malawi
United States