New drugs for preventing Plasmodium vivax-type malaria, but not for curing.
29 March 2016
More than half of the malaria cases outside Africa is caused by the malaria parasite Plasmodium vivax. A complication in the treatment is the presence of dormant stages in the liver that after weeks to years can cause a new malaria attack in the blood and thereby disease. There is a single drug available that is only effective after a long treatment regime. This drug has serious side effects in large groups of people. Therefore more research is needed to develop new treatments against these dormant parasite stages.
Currently, a culture system suitable for large scale drug testing against Plasmodium vivax vivax is lacking. This can only been done using a closely related simian malaria parasite, Plasmodium cynomolgi. This parasite has many biological similarities to the human parasite, including the formation of dormant stages. Previously BPRC researchers have developed an in vitro test in which they were able to determine the activity of drugs against dormant stages. (http://www.bprc.nl/en/article/a-new-method-for-testing-the-activity-of-drugs-against-dormant-malaria-parasites) In this assay, a compound was identified that was highly active against all liver stage malaria parasites, including the dormant stages. The researchers have now tested this drug for in vivo activity in rhesus monkeys.
They determined the activity of the drug at two different times during the infection. Administration of the compound shortly after the injection of the parasite was found to fully prevent the parasites entering the blood. However, administration at a much later timepoint in the infection did not have any measurable effect on the older dormant stages; these dormant forms could start developing again and give rise to a new blood infection. This work shows that the current in vitro test can identify compounds that prevent malaria, but the assay is not predictive for activity against existing infections. Further optimization of the in vitro test is needed in order to enable in vitro testing of compounds that are active against older dormant stages, before drugs are tested in vivo vivo in monkeys. This work was published in the journal Antimicrobial Agents and Chemotherapy (http://aac.asm.org/content/early/2016/02/23/AAC.03080-15.long)