Malaria parasites survive in difficult times by not being too sticky.
During the dry season in Africa, when mosquitoes are scarce, malaria parasites have difficulty spreading to new hosts. Thus, the parasites hide in the human body by keeping the infecting cells clinging to the blood vessels, the researchers reported on October 26 in Nature Medicine. In this way, infected cells are removed from the circulation and parasite levels in the body remain low, making people less sick and allowing the parasite to persist undetected.
Doctors have long observed that the symptoms of malaria, a deadly mosquito-borne infection, tend to wane during the dry season, which runs from January to May. But the reason was not clear.
Keeping a low profile during the dry months is a successful strategy for the parasite, says Martin Rono, a parasitologist at the KEMRI-Wellcome Trust in Kilifi, Kenya, who did not participate in the work. Knowing how malaria parasites persist without causing disease, until mosquitoes return to move the organisms of an infected person to the next victim could help control malaria during the dry season.
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Plasmodium falciparum, the parasite responsible for malaria, infects red blood cells as part of a complex life cycle. Once inside a cell, the parasite produces proteins that dock to the outside of the cell and cause it to stick to blood vessels so that it is not carried to the spleen, where it would otherwise be removed from the body.
Usually, only the first stages of the parasite's life circulate in the blood, while older parasites thrive inside the red blood cells attached to blood vessels, says Silvia Portugal, a biologist who led the work at Heidelberg University Hospital in Germany. “That’s a textbook, so it was very surprising” to see that the parasites from the dry season behaved differently in the lab, he says, the cells didn’t stick.
Portugal, now at the Max Planck Institute for Infectious Biology in Berlin, and colleagues identified around 600 people in Mali infected with malaria in 2017 and 2018. First, the team ruled out two other ideas to explain the seasonality of the parasite: genetic diversity and immunity. The team found that genetically distinct parasites did not reach in different seasons, nor did the host’s immune system suppress the growth of the parasite.
But when the researchers compared which genes were turned on or off in samples taken from asymptomatic people in the dry season and symptomatic people in the wet season, they found that 1,607 genes had distinct seasonal patterns. In the dry season, 1,131 genes that were inactivated in wet season parasites were activated. Another 476 were inactivated in dry season parasites, suggesting that when the wet season ends, P. falciparum may alter its genetics to make red blood cells less sticky. This allows the parasite to replicate and persist without triggering alarms that alert the immune system to fight infection.
Malaria-infected blood cells use certain proteins to adhere to blood vessels almost like velcro, Portugal says. The loss of adhesion could be due to the parasite producing less of these proteins or because the proteins are different in some way.
However, it is not yet clear which specific genes are involved in the change. One of the issues is that the researchers compared parasites from two different vital stages, says Abdirahman Abdi, a parasitologist also from the KEMRI-Wellcome Trust. To reduce genes that can affect adhesion, he said, researchers may have to compare genetic activity in parasites at the same stage.