A transport system used by the malaria parasite to infect blood cells could be a target for new treatments, scientists have said.
Not all mosquitoes carry the malaria parasite
Australian and US teams both claim that they have pinpointed the key proteins involved in the process.
These proteins are transported into the cell to establish infection. Some cause damage and others help the parasite avoid destruction, they believe.
The findings are published in the journal Science.
Before now, scientists had not known exactly how these events occurred.
The researchers at the Northwestern University in the US, and another team at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, looked at the most harmful form of the four human malaria parasites - Plasmodium falciparum.
This parasite kills over 1m children each year and is responsible for at least a fifth of Africa's infant deaths, according to the World Health Organization.
The scientists looked at the parasite's genes to find out what was happening.
The parasite enters the human when an infected Anopheles mosquito bites and sucks up blood.
Once inside the human host, the parasite undergoes a series of changes.
It enters the blood cells and takes up residence so that it can replicate itself and multiply.
Once inside the blood cell, the parasite releases or exports proteins that modify the structure of its new home to suit its tastes.
These proteins have special properties that allow them to travel across not only the parasite's protective coat or membrane, but also the membrane of the blood cell in some instances.
Some of these special proteins are also thought to cause the symptoms of malaria, such as fever and muscle aches.
A particular protein, called PfEMP1, enables the parasite to stick to red blood cells, thus preventing its clearance cleared from the body.
Dr Alan Cowman, head of the Australian team, said: "We have tried removing certain proteins from the parasite and the parasite survived well in most cases.
"So those proteins were not useful drug targets.
"But some of the exported proteins are unique to Plasmodium species, and identifying them has been a major step forward in establishing which are the important ones."
He said it might now be possible to develop treatments to target these proteins.
Dr Colin Sutherland, a malaria expert at the London School of Hygiene and Tropical Medicine, said: "There are two key strategies against malaria that may be assisted with this new information.
"Firstly, the proteins that reach the outside of the red blood cell interact directly with the human immune system and may be useful targets for future vaccines.
"Secondly, because we know that these proteins are transported into the red blood cell, they are much easier to reach with circulating drugs than targets hidden within the parasite's membrane cloak."
He said the fact that the majority of the proteins bear no resemblance to any known human proteins was good because it means any drugs that are found to target these molecules are unlikely to adversely affect the human host.