There are different types of malaria parasites but for humans Plasmodium falciparum and Plasmodium vivax are the most relevant ones. P. falciparum because it causes severe disease and P. vivax because this parasite can remain silently present in the liver.

These ‘dormant’ parasites (“hypnozoites”) are invisible to the immune system and while they are sleeping they do not cause disease. However, there is always the risk that these parasites wake up and cause a new malaria infection. Current antimalaria drugs are not effective in preventing these malaria relapses. Therefore, hypnozoites form a hidden reservoir in the population, and they complicate malaria control and elimination. Worldwide much emphasis is put on drug-development for hypnozoites.

In humans it is not possible to study hypnozoites, therefore we use the Plasmodium cynomolgi model. P. cynomolgi mirrors the human malaria parasite P. vivax biology, including the formation of hypnozoites, but it infects rhesus monkeys.

Cracking the code of dormant malaria parasites

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The P. cynomolgi model offers possibilities to find new drugs against the dormant liver stage malaria. Together with partners from Singapore and Basel, we have increased our knowledge of the genetic characteristics of this parasite form. Using state of the art technologies, we have shown that the parasite, when deep asleep, still has some activities, albeit at a low level. This information will be used to identify potential targets for new medicines to prevent malaria relapse in people that carry hypnozoites.

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Detecting the presence of dormant malaria parasites

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Currently there is no diagnostic test to detect hypnozoites, the dormant malaria parasites in the liver. If, and when, new medicines are available to wipe out hypnozoites such a diagnostic test is necessary to identify patients that require treatment. Together with Japanese colleagues, we are pioneering the development of a diagnostic test for hypnozoites. For this we use our hypnozoite in vitro culture model. The test is based on subtle changes in specific molecules from the host cell after infection with a hypnozoite. The results of initial small-scale tests are promising and will be followed up in 2019 with larger scale analyses.

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