The Centers for Disease Control and Prevention estimated that there were 212 million cases of malaria across the world in 2015, and 429,000 of those people died — mostly children living in Africa. Preventing and treating those infections has been a challenging world priority. That makes a new malaria drug discovery — published in Science Translational Medicine — incredibly important.
A team of international researchers, led by Kelly Chibale at the University of Cape Town in South Africa, have developed a drug they call MMV390048, which is effective against resistant strains of the malaria parasite, works to kill the malarial parasite in any stage of its life cycle, and only requires one dose.
Four kinds of malarial parasites infect humans — Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae — and all of their life cycles involve two hosts, a Anopheles mosquito, and a human. Different stages of the life cycle are played out in the mosquito and humans, but all are important for transmission. Ultimately, the Anopheles mosquito picks up the parasite from one infected person and delivers it to another, spreading the infection.
Right now, a combination of drugs — usually including a quinine-type drug — is used to treat the infection, but the parasite is becoming increasingly resistant and some forms of malaria can reactivate after years of being dormant inside the body.
Scientists are set to test the world's first malaria vaccine — which was specifically created to fight the most deadly type of malarial parasite, P. falciparum — in a handful of African countries in 2018.
That sounds like promising news, and it certainly is a big step in eradicating the disease, but the efficacy of the new vaccine depends on proper administration — to be given is in three primary doses, then a booster 18 months later. And even when properly administered, in a clinical trial of 15,459 infants and children, only about 50% fewer children contracted the disease over four years.
So, the vaccine seems to be partially effective and won't prevent infections with all types of the malarial parasite. The world needs a single-dose malaria treatment that will bring relief to the millions of infected people. Maybe MMV390048 can fill that need.
MMV390048, the new drug developed by Chibale and colleagues, has been tested in rodents and monkeys infected with malaria. The researchers saw a decrease in transmission between malaria-infected mice when they were treated with MMV390048 and exposed to Anopheles mosquitoes. Monkeys treated with the drug and then injected with malaria didn't develop the disease.
The drug doesn't just protect against infection but can help kill the parasite in blood, too. MMV390048's target inside malaria cells is a protein kinase. The action of MMV390048 to block this protein killed P. falciparum infection in human red blood cells in lab experiments, but did not completely kill the parasite stage of P. vivax infecting liver cells.
The results were very encouraging, but the drug still needs to be tested in humans, including trying higher doses that might kill all the stages P. vivax.
The ability of MMV390048 to block all life cycle stages of the malaria parasite, offer protection against infection as well as potentially block transmission of the parasite from person to person suggests that this compound could contribute to the eradication of malaria, a disease that claims the lives of several hundred thousand people every year.
That puts a lot of pressure on MMV390048 developed by Chibale and colleagues. A half a million lives a year could depend on it.
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