Malaria parasites develop in the lymph nodes of the immune system, researchers have discovered.
The malaria parasite is spread by mosquitoes
Scientists say the finding was unexpected, and underlines just how complex malaria infection can be.
The immature parasites are known to travel to an infected person's liver, which, until now, scientists thought was the only place they could develop.
The study, by Pasteur Institute in Paris, features online in the journal Nature Medicine.
Small bean-sized organs made up of densely packed lymphocyte cells
Clusters are widely distributed in the body
Essential to the functioning of the immune system
The main sites where immune responses are launched
The researchers hope their work could aid the development of better vaccines, which might potentially target the parasites before they develop in the liver.
The researchers infected mosquitoes with fluorescently tagged Plasmodium parasites, and then allowed the mosquitoes to bite a mouse.
From each mosquito bite, they found an average of 20 fluorescent parasites embedded in the animal's skin.
The parasites were found to move through the skin at high speed in a random, circuitous path.
After leaving the skin, the parasites frequently invaded blood vessels.
This was no surprise as they need to travel through blood vessels to get to the liver.
However, about 25% of the parasites invaded lymphatic vessels of the immune system, ending up in the lymph nodes close to the site of the bite.
Their journey seemed to stop there, as the malaria parasites almost never appeared in lymph nodes farther away.
Within about four hours of the mosquito bite, many of the lymph-node parasites appeared degraded.
They were also seen interacting with key mammalian immune cells, suggesting that the immune cells were destroying them.
A small number of the parasites in the lymph nodes, however, escaped degradation and began to develop into forms usually found only in the liver.
By 52 hours after the mosquito bites, no parasites remained in the lymph nodes, which suggests that they cannot develop completely there.
Lead researcher Dr Robert Ménard said only fully developed parasites can infect red blood cells and cause malaria - so the lymph-node parasites probably do not contribute to the appearance of malaria symptoms.
However, he said even partially developed or destroyed parasites could significantly affect how the immune system responds to infection.
Parasites developing in the lymph nodes might alert the body that an invader is present, and activate a protective immune response.
Alternatively, their presence might desensitise the body to the parasites, blunting the immune system's response to infection.
The researchers were also surprised to find that some of the parasites remained in the animals' skin for up to seven hours, raising the possibility that they might be responsible for a second wave of infection.
Professor Brian Greenwood, of the London School of Hygiene and Tropical Medicine, agreed that the study would help scientists better to understand the immune response to malaria.
He said it had previously been thought that infection levels at the time when a mosquito bites were too small to trigger an immune response, which only came once the parasites started multiplying in the liver.