Monday, 5 December 2011

Life Cycle of Malaria Parasites – A New Twist

The life cycle of Plasmodium spp., agents of malaria, is one of the harder ones for a parasitology student to grasp. It’s full of difficult words such as gametocyte and shizogony, and involves multiplication in both humans and mosquitoes - two hosts about as different from each other as one could imagine. Likewise, the immune system is so complex that most people can only achieve a basic understanding.

Recently, both of these things got more complicated as researchers discovered how malaria may evade the immune system and thereby survive for long periods and cause new bouts of illness later. Aha! Some old mysteries have been solved, but parasitology students will likely groan.

Two species of Plasmodium, P. vivax and P. ovale, have long been known to remain hidden away in the human liver after an initial episode of malaria, returning to the blood weeks, months, or even years later to start the infection all over again. Two other species, P. falciparum and P. malariae, do not stay within liver cells (hepatocytes) but can still mysteriously reappear after all parasites have disappeared from the blood. Where do these parasites, thought to multiply in humans only in red blood cells and hepatocytes, go? At last, we think we know.

A paper by Michelle N. Wykes et al reports that plasmodia can hide within dendritic cells—white cells that are an important part of the immune response intended to eliminate these parasites - in the spleen, multiply inside the cell and return to the bloodstream later to reinitiate malaria (“Rodent blood-stage Plasmodium survive in dendritic cells that infect naive mice.PNAS 2011).

[caption id="attachment_360" align="alignleft" width="300" caption="Dendritic cell, image by Judith Behnsen et al, Creative Commons 2.5"]Dendritic cell[/caption]

Plasmodium spp. are not the first parasites known to use the host’s immune system against it in this way: Leishmania sp. parasites invade macrophages, an immune cell intended to kill them, and multiply within the cell before bursting out and spreading to other cells in the body. Other parasites, such as the schistosomes and trypanosomes, trick the immune system in other ways.

This discovery will have implications for the treatment of malaria. Not only will it offer new possible targets for drug therapy or vaccine, it will oblige us to take these infected white cells in the spleen into account in treating infections. The authors suggest that parasites within the dentritic cells may be in a state of “arrested” development and thus able to live a long time before reappearing. I’m wondering what role these arrested parasites might have in the development of drug resistance in Plasmodium spp. parasites.

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