The development of an in vitro test system for ‘dormant’ malaria parasites

Plasmodium vivax is the most widely distributed cause of malaria in humans. This parasite can generate ‘dormant’ forms in the liver, the so-called hypnozoites. Hypnozoites can remain dormant for years and then ‘wake up’ through unknown mechanisms, causing disease. Only one active drug against hypnozoites is available. However, this drug causes serious side effects in a large number of people. Research towards new drugs is complicated because of the lack of a good in vitro system for P. vivax.

Researchers of the department of Parasitology at the BPRC are working with Plasmodium cynomolgi. This monkey malaria parasite is closely related to P. vivax and also forms hypnozoites. In collaboration with researchers from France, a culture system has been developed in which livercells derived from rhesus macaques can be infected with P. cynomolgi parasites (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0018162).

After treating the cultures with drugs that are inactive against hypnozoites only small malaria parasites remained present. These small forms disappeared after treament with the anti-hypnozoite drug. This confirms the presence of hypnozoites in these cultures and for the first time enables large scale in vitro screening of compounds against hypnozoites. Subsequently, a selected subset of drugs can be tested in animal models. This new method will result in a reduction in the use of experimental animals.