Killing the liver-stage malaria parasite with baculovirus: a drug

Killing the liver-stage malaria parasite with baculovirus: a drug

Killing the liver-stage malaria parasite with baculovirus: a drug

Currently, few antimalarial treatments exist that effectively kill liver-stage malaria parasite Plasmodium vivax, which can lay dormant for months or even years. Researchers have reported a new drug that could eliminate liver-stage malaria parasites completely. Using an insect virus, known as a baculovirus, the researchers investigated the ability of baculovirus to mediate innate immunity against malaria infection. This work could pave the way for developing new and more effective antimalarial treatments.

A proportion of P. vivax sporozoites differentiate to a hypnozoite form that ultimately reactivates and proliferates leading to a blood-stage relapse. The hypnozoites are not eradicated by artemisinin and can awaken months to years after the last bout of clinical malaria, unless a drug specifically targetting the hypnozoite, primaquine, is administered. However, primaquine has severe side effects.
Credit: Kanazawa University
 
Currently, few antimalarial treatments exist that effectively kill liver-stage malaria parasites, which can lay dormant for months or years as in the case of Plasmodium vivax. Researchers from Kanazawa University have successfully demonstrated that administration of a baculovirus virion (BV) completely eliminates liver-stage parasites in a mouse model via BV-induced fast-acting innate immunity. Further development of BV-based drugs could lead to 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 where it infects red blood cells. Symptoms normally appear a few days or weeks later, but in the case of P. vivax, the parasites can also lay dormant in the liver with disease recurring months or even years later (known as hypnozoites). P. vivax is the most widely distributed human malaria parasite in the world (a major health risk to 2.85 billion people worldwide). The active blood-borne form of P. vivax can be targeted with artemisinin, but only a single drug, primaquine, is available for the hypnozoites.

However, primaquine is associated with a high risk of life-threatening hemolytic anemia in people with glucose-6-phosphate-dehydrogenase enzyme deficiency. In addition, even effective doses can cause 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.” says 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.”

 

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