24 THE SCIENTIST | the-scientist.com
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t’s not clear w hy, 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. fal-
ciparum 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 s ay,
‘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 world-
wide mortality rates in the second half of
the 20th century.
In the 1990s, artemisinin—a com-
pound derived from the wormwood plant
that was used for centuries in natural med-
icine 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 aggres-
sive, short-acting artemisinin derivatives
with longer-acting partner drugs to make
artemisinin-based combination thera-
pies (ACTs). These extremely effective
treatments—plus intensive programs forimplementing 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).
Starting around 2007, however, ACT
resistance slowly began creeping into
parasite populations, especially in the
Greater Mekong. These days, there is at
least one P. falciparum mutant resistant
to each ACT partner drug, and a hand-
ful have begun to show partial resistance
to artemisinin itself, with the drug tak-
ing longer to clear the parasites from the
bodies of infected people. “This truly is
a wily parasite,” says biochemist David
Kaslow, director for the PAT H MalariaThe microorganism that causes malaria has evolved resistance
to medicine’s front-line therapies before. Can it do it again?BY NATALIE SLIVINSKI