Fatal Fever Caused by Waste By-product of Malaria Parasite's Reproductive Process

A Canadian stidy has said that by studying a crystal-like by-product released during reproduction among parasites from the Plasmodium family, we may be able to understand why malaria leads to devastating inflammation and fever.

Lead researcher Dr. Martin Olivier, of McGill University in Montreal, points out that, inside the human body, the malaria parasite infects red blood cells where it survives and reproduces by feeding on the cells' contents.

Eventually, says the researcher, the cells burst and release the parasites and hemozoin.

"Our results describe the mechanism by which the hemozoin activates the immune system, resulting in the production of inflammation mediators and in the high fever that we witness in malaria patients," said study's first-author Dr. Marina Tiemi Shio, of the Research Institute of the McGill University Health Centre (RI-MUHC).

According to the researchers, hemozoin is first ingested by "cleaning" cells called macrophages, which leads to a chain reaction ending in the activation of the inflammasome: an important structure inside immune cells which lead to inflammation.

They say that the activation of the inflammasome leads to the production of the body's fever mediator, interleukin beta (IL-beta).

"Our work is a milestone in that it is the first study that reveals the enzymes that act as intermediary between the hemozoin and inflammasome. Now our picture of the process that goes from infection to fever is more or less complete," said Dr. Olivier.

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"On the other hand, we also proved that malaria is too complex to be narrowed down to one single mechanism. In the absence of either IL-beta or a functional inflammsaome, the development of the disease is delayed but not completely stopped. Although the discovery of this relationship is important, there are other mechanisms at work," he added.

Even though scientists have been familiar with the mechanisms that go from the activation of the inflammasome to the onset of the malaria symptoms, none of the previous studies has ever shown the beginning of the process.

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"These results prove the primary role hemozoin plays in the development of malaria, and designates it as a favoured choice for future innovative treatments," said Dr. Olivier.

The researchers believe it will be possible to familiarize the immune system to small quantities of hemozoin, and diminish the inflammatory response in the event of infection, according to a principle similar to that of vaccines.

The results of the study have been published in the journal PLoS Pathogens.

Source-ANI
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