Why do parasites harm their hosts?
That's a question evolutionary biologists ask as they try to predict how a parasite might evolve and perhaps become more lethal in response to control methods, such as vaccines or drug treatments.
A new study based on mathematical modeling reveals how tradeoffs faced by human malaria parasites (Plasmodium falciparum) - between using resources to replicate within hosts and transmitting to new mosquito and human hosts - might limit their virulence.
"We need to understand what constrains their evolution in the first place before we can make good predictions about what will happen in response to control measures," said Megan Greischar, assistant professor of ecology and evolutionary biology in the College of Agriculture and Life Sciences (CALS) and senior author of the study.
The study was published Nov. 25 in Evolution.
Malaria parasites, P. falciparum, have a complicated life cycle, split between mosquito and human hosts. When an infected mosquito bites a human and spreads the parasites, they multiply in liver cells before entering red blood cells in the bloodstream. There, parasites replicate asexually before bursting out, killing the cells.
This replication phase in red blood cells can cause human hosts to feel sick. But replicative stages cannot infect mosquitoes. Instead, some parasites in the blood differentiate into sexual transmission stages, called gametocytes. When gametocytes circulate in the blood, they can infect mosquitoes when the insects feed. The parasites then continue their life cycle inside the mosquitoes.
The replication phase, inside red blood cells, and transmission stage where gametocytes are produced can occur at the same time, so investing in one limits the parasite's ability to invest in the other.
Most mathematical models that investigate parasite evolution assume a tradeoff between the rate of transmission to new hosts and the duration of the infection within a host. But in this study, the researchers did not assume this tradeoff and instead incorporated the impact of a human host's immunity, which mainly targets replication stages within red blood cells. Then, they looked to see what tradeoffs occurred.
They found that since the parasite's investment into producing transmission stages (gametocytes) limits its ability to reproduce within red blood cells, greater investment into transmission reduces capacity to infect the host for longer periods.
"If they over-invest in the transmission stages, which are absolutely required for them to spread, then they will not be able to persist within the host as effectively," Greischar said. The study revealed a pattern opposite to that expected with a transmission-infection duration tradeoff, where prudent reductions in transmission investment increased both the potential rate and duration of transmission.
Parasites with higher transmission investment must devote less toward replicating within the host, which in turn makes them less harmful.
Parasite success or fitness is ultimately determined by how well it spreads to new hosts. The current model revealed that this tradeoff constrains parasite fitness and leads to less investment in transmission than predicted to be ideal by previous models, a result that more closely matches data found in actual, real-world infections, Greischar said.
Denis Patterson at Durham University in the United Kingdom is the study's first author. Co-authors include Lauren Childs at Virginia Tech, Isaac Stopard at Imperial College in London, United Kingdom, Nakul Chitnis at the University of Basel in Switzerland and Sergio Serrato-Arroyo at Arizona State University.
The study was funded by CALS, the Durham Biophysical Sciences Institute, the National Science Foundation and the Gates Foundation.
