Malaria’s Advance Preparations for Infecting a Host

Seconds after a malaria-infected mosquito bites, the sporozoite form of the parasite navigates to the host’s liver. Here it stays embedded until thousands of infected cells burst into the bloodstream, launching malaria’s deadly blood-stage infection. In a study published today in Nature Communications, scientists from Seattle Children’s Research Institute describe how malaria Plasmodium parasites prepare for this journey as they lie in wait in the mosquito’s salivary glands.

“Essentially the parasite makes a blueprint of the proteins it needs to infect the liver while still in the mosquito, far in advance of actually making the proteins once in the human,” says senior author Stefan Kappe. “It’s cool biology that offers new insight into how we might begin to stop the parasite from infecting the liver.”

Malaria sickens over 300 million people and kills around 435,000 people worldwide every year, but there is still no effective vaccine to protect against it. In the new study, the researchers focused on understanding the complex biology of the malaria parasite and the host immune response to infection, as well as exploring new strategies to protect against the multiple stages of infection.

“We found that the sporozoites make and store all these plans for proteins, but then don’t actually make the protein,” says coauthor Kristian Swearingen. “It’s the first window into a process in which the proteins are only made once the parasite negotiates the liver environment, suggesting the proteins are needed for the parasite to infect the human.”

This strategy gives the malaria parasite the adaptability it needs to launch its attack seconds after the mosquito bites. “The parasite has planned ahead, gathering the tools it needs to infect the human while it’s sitting in the mosquito waiting for this unpredictable event to happen,” Kappe adds. “It may exist in this prepared state for days or even weeks until it has the opportunity to strike in the human, so it has to be ready whenever this moment comes.”

According to Swearingen, the blueprint revealed in their research may ultimately lead scientists to new ways to disable the parasite. “Any of these proteins that are critical for the parasite to invade the liver could serve as potential targets for new malaria drugs or vaccines,” he says. “With effective tools, we could see a day where malaria is completely eradicated.”