Malaria places an enormous burden on low income countries, infecting over 200 million people each year and killing approximately 500,000 children under 5, primarily in Sub Saharan Africa. Despite decades of study, it remains unclear why some children suffer from very severe disease whereas others have almost no symptoms at all; some infections are acute and some last for months or even years. Studying the parasite in the lab is challenging because it must be grown in human red blood cells, and it remains virtually impossible to study the parasite during infection in the human bloodstream. However, using mathematical models we can examine the likely impact of experimental findings on the growth of the parasite during infection.
We have developed within-host mathematical models to examine how host and parasite variation can drive different disease outcomes in malaria. Together with molecular biologist Professor Manoj Duraisingh, we have been parameterizing our models using data from in vitro work to understand how different parasite strains interact with red blood cell variation (for example, variation caused by the fact that red blood cells age over their 4 month lifespan, changing considerably as a target for parasite invasion). We have previously shown that within-host dynamic processes of this kind can:
- Explain why a malaria parasite of macaques has started causing severe disease in humans (Lim et al. 2013)
- Modulate the trade-off between virulence and transmission among parasites (Coleman et al. 2014)
- Identify the important knowledge gaps that remain in our understanding of human immunity to malaria (Childs and Buckee, 2015)
- Cause the parasite to adapt efficiently, paradoxically so in low transmission settings (Chang et al. 2016)
- Alter the predicted effect of interventions on a population level (Hansen and Buckee, 2013)
We are continuing our work in this area with Prof. Duraisingh to examine the impacts of red blood cell polymorphisms and parasite adaptation on disease outcomes in malaria.
Collaborators: Manoj Duraisingh (Harvard)
Funding: Burroughs Wellcome Fund