Combination therapies composed of new antimalarial therapeutics with
distinctly different parasite targets and mechanisms of action are the best tools to enhance
treatment of uncomplicated falciparum malaria and delay the appearance and expansion of
drug resistant malaria. The efficacy of artemisinin combination therapies is the most
relevant criteria for evaluating drug combinations. The demonstrated values of an ACT to
improve clinical outcomes and delay emergence and spread of parasite drug resistance
were all factors in the decision by the WHO to recommend that ACTs be used as the best
treatment for treating uncomplicated infections with P. falciparum malaria in Asia and
Africa. As discussed in the last chapter, the list of recommended ACTs includes
dihydroartemisinin-piperaquine, artemether-lumefantrine, artesunate-mefloquine,
artesunate-sulfadoxine-pyrimethamine, and artesunate-amodiaquine. All of these
combinations have been shown to be efficacious; however, efficacy of an ACT is affected
by resistance to either drug partner. The cost of artemisinin analogues derivatives is a
significant contributor to the increased cost of ACT treatment courses. A research project
called the artemisinin project was initiated to develop an inexpensive method of semisynthetic
production of artemisinins through fermentation rather than deriving artemisinin
analogues by extracting artemisinin from the sweet wormwood plant. A cheaper
manufacturing method will make ACTs more affordable, and it will be possible to increase
distribution to patients in need. Innovations that facilitate production of cheaper ACTs will
enhance the odds of a full recovery from falciparum malaria infections with decreased side
effects and limit the emergence and spread of drug resistant parasites. Through vigorous
efforts to enhance manufacture of inexpensive artemisinins coupled with improved
prescription and enhanced patient compliance, the artemisinin drug combinations may still
be effective for decades to come.
Keywords: Action mode, adverse effects, Artemether- lumefantrine, artesunateamodiaquine,
artesunate-mefloquine, clinical recovery, dihydroartemisininpiperaquine,
low cost, parasitological cure, therapeutic efficacy.