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Baculovirus virion thoroughly removes liver-stage parasites in mouse model

At the moment, few antimalarial treatments exist that effectively eliminate liver-stage malaria parasites, which can lay inactive for several months or years as in the case of Plasmodium vivax. Researchers from Kanazawa University have successfully shown that administration of a baculovirus virion (BV) completely gets rid of liver-stage parasites in a mouse model via BV-induced fast-acting innate immunity. Further development of BV-based drugs could result in newer and more effective treatments for malaria.

Malaria is caused by Plasmodium, a parasite spread by the Anopheles mosquito as it feasts on blood. The parasite is released into the bloodstream and travels to the liver to mature, before being released back into the bloodstream wherein it infects red blood cells. Symptoms typically appear a few days or weeks later on, but in the case of P. vivax, the parasites can also lay dormant in the liver with disease recurring several months or even years later (referred to as hypnozoites). P. vivax is one of the most widely distributed human malaria parasite worldwide (a major health risk to 2.85 billion people worldwide). The active blood-borne form of P. vivax can be targeted with artemisinin, however only one drug, primaquine, is readily available for the hypnozoites.

Nevertheless, primaquine is associated with a high risk of life-threatening hemolytic anemia in people with glucose-6-phosphate-dehydrogenase enzyme deficiency. Furthermore, even effective doses can trigger several side effects including nausea and vomiting. "Malarial infection affects a large number of individuals each year, many of whom are young children aged under five." states first author Talha Bin Emran. "Current treatments can have serious side effects for some individuals, hence safer radical curative drugs that efficiently kill the hypnozoites are urgently needed."

Using BV, the researchers conducted a number of experiments with a mouse model of malaria. They verified that intramuscular administration of BV not only provides complete protection against a subsequent sporozoite infection but at the same time eliminates existing liver-stage parasites completely, which could prevent or reduce the severity and complications of the disease. The eradication of liver-stage parasites with BV was superior to that with primaquine. Additionally, they showed that the elimination effect occurred in a TLR9-independent manner. These effects were mainly mediated by a cytokine known as interferon alpha (IFN-α), which has previously been examined as a treatment for several other diseases.

Additional work is needed to confirm the results in primates and eventually humans, but preliminary results suggest that there are a number of potential advantages of BV as a new non-hemolytic single-dose substitute to primaquine. "Currently P. vivax patients must receive several doses of antimalarials for treatment, consequently adding BV to existing drugs could reduce the risk of infection while receiving treatment." study corresponding author Shigeto Yoshida says. "It could also provide protection against the disease in the liver. There are a number of challenges in the treatment of malaria, which we hope to overcome with our work." These results demonstrate the potential to develop new malaria drugs that kill P. vivax hypnozoites over an extended period and with reduced side effects.


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