What happens right after an infected malaria mosquito bites you, but before you feel sick and show symptoms? The moment a female Anopheles mosquito bites, she injects tiny Plasmodium sporozoites into the bloodstream. At this point, you might feel nothing at all. That’s because the parasite’s first stop is your liver, where it begins a silent but critical stage of its life cycle.

Sporozoites on the move

Sporozoites are the fastest and most specialised forms of Plasmodium. Within minutes of entering the bloodstream, they travel to the liver, guided by chemical signals and surface molecules that help them locate liver cells, known as hepatocytes. Once there, they slip inside the liver cells, avoiding immune defences and establishing a hidden stronghold where they can multiply without detection.

Once there, they slip inside the liver cells, avoiding immune defences and establishing a hidden stronghold where they can multiply without detection. Inside these cells, the parasites surround themselves with a protective membrane that shields them from the body’s immune attack. The liver itself is an organ that tolerates many foreign substances as it filters blood, which makes it an ideal hiding place. Together, these factors allow the parasites to remain invisible while they grow and prepare for the next stage of infection.

Silent multiplication

Inside each infected hepatocyte, the parasite grows and divides for several days. During this “liver stage,” no symptoms appear. The parasite produces thousands of new merozoites in preparation for the next phase, which involves the invasion of red blood cells.

This incubation period varies from species to species. For P. falciparum, it typically lasts about 7–10 days, while P. vivax and P. ovale may linger much longer. These last two species can form dormant liver stages called hypnozoites, which can remain hidden for months and sometimes even years before reactivating and causing a relapse. This clever adaptation makes elimination more challenging and explains why some people can fall ill long after leaving a malaria-endemic region.

The asymptomatic stage matters

Because the liver stage causes no symptoms; infected individuals don’t know they are carrying the parasite. Yet, this silent phase is essential for malaria transmission: it gives the parasite time to multiply, ensuring that when it finally enters the bloodstream, there are enough parasites to maintain the infection and continue the cycle.

Understanding the liver stage is critical for developing treatments and vaccines that can stop the parasite before it spreads, rather than waiting until symptoms appear.

Controlling Plasmodium during the liver stage requires targeting the parasite before it reaches the blood. Sporozoites can be intercepted with prophylactic antimalarial drugs taken before and during exposure, preventing them from invading liver cells. For species that form dormant hypnozoites, such as P. vivax and P. ovale, liver-stage–specific are essential to eliminate these hidden parasites and prevent relapses. Developing vaccines that block sporozoites from entering the liver is another promising strategy currently under study.

In the next article we follow Plasmodium as it leaves the liver, invades red blood cells, and begins the cycle that causes fever, chills, and anaemia; the unmistakable signs of malaria.

Click here to read the entire series.