Artemisinins are the only currently available mainstream drugs that do not have
widespread issues with P. falciparum drug resistance outside of Southeast Asia. Initial reports
of artemisinin resistance were noted in western Cambodia near the border with Thailand in
2009 and a possible molecular marker was identified in 2014. For other traditional
antimalarial therapies, malaria resistance has been observed to be highly variable and the
geographical distribution of resistance and rate of spread have varied significantly. The times
for resistance to appear have varied from 278 years for quinine, 35 years for the artemisinins,
12 years for chloroquine, 5 years for mefloquine, 1 year for proguanil, and less than 1 year for
sulfadoxine-pyrimethamine and atovaquone. Given the emergence of artemisinin resistance
and the possibilities of the spread of resistance out of the border regions of Cambodia, it is
essential to prevent the loss of artemisinin combination therapies (ACTs) which are the
current first-line treatments for malaria. The use of drugs in combination for treatment of
malaria is the best tool to decrease the incidence and spread of malaria drug resistance. The
rationale for this approach is threefold: 1) drug combinations are often more effective than
monotherapy with one drug; 2) artemisinins substantially reduce gametocyte carriage and
thus reduce transmission; and 3) if a mutation arises in a malaria parasite during treatment
with one drug, this parasite should still be killed by the partner drug. As each drug protects the
other, resistance should be discouraged from occurring. An antimalarial drug combination
must provide partners which are each independently capable of treating the disease. In
addition, drug combinations used to treat malaria such as the ACTs often provide radical
cures of malaria when administered in a 3-day treatment regimen, which also provides
protection against emergence of artemisinin resistance.
Keywords: Artemisinin-based combination therapy (ACT), artemisinins,
chloroquine, drug combination, malaria, malaria infection, malaria parasite,
malaria transmission, mefloquine, proguanil, resistance, resistant spread.
