Date: 05.03.2019

Are We Headed for a New Era of Malaria Drug Resistance?

Plasmodium falciparum has shown an ability to evade everything we throw at it, most recently artemisinin-based combination therapies, today’s front-line treatment.

IN THE BLOOD: Red blood cells infected with a malaria parasite (purple) circulate with uninfected RBCs (gray).

It’s not clear why, but the Greater Mekong Subregion—Cambodia, southern China, Laos, Myanmar, Thailand, and Vietnam—is a major source of malaria drug resistance. Each time a drug has been deployed in the area, resistance mutations in local Plasmodium falciparum, the parasite that causes the mosquito-borne disease, have followed close behind. Parasites there seem more adaptable than P. falciparum in other regions, says Thanat Chookajorn, an assistant professor of biochemistry at Mahidol University in Thailand, who studies the molecular genetics of malaria parasites that thrive in the Greater Mekong.

“It sounds kind of self-centered to say, ‘My parasite’s the worst in the world,’” Chookajorn says. “But I would say that there’s definitely something funny going on with this population.”

Resistance to chloroquine, the first widely used antimalarial drug, first arose in the Greater Mekong shortly after World War II. Chloroquine-resistant strains eventually spread to Africa, which carries more than 90 percent of the global malaria burden. This explosion of drug resistance contributed to an alarming climb in worldwide mortality rates in the second half of the 20th century.

In the 1990s, artemisinin—a compound derived from the wormwood plant that was used for centuries in natural medicine to treat pain and fever—was released globally as a new malaria treatment.1 The drug was a boon to malaria scientists, who were able to pair brief pulses of aggressive, short-acting artemisinin derivatives with longer-acting partner drugs to make artemisinin-based combination therapies (ACTs). These extremely effective treatments—plus intensive programs for implementing rapid diagnostic tests and insecticide-impregnated bed nets—slowed the parasite’s progress. Between 2010 and 2015, global malaria mortality dropped almost 30 percent. Compared to nearly 1 million annual malaria-related deaths in the late 1990s, today only about 400,000 of the 220 million cases per year end in the patient’s death, according to the World Health Organization (WHO).

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