**3.2 Shift to multiple first-line therapies in malaria treatment**

Shift from monotherapy to multiple first-line therapies in malaria treatment, e.g., use of artemisinin-based combination therapy (ACTs) has been exploited as an intervention to alleviate resistance to several antimalarial monotherapies [87], and according to [88], the adoption of ACTs was as a result of occurrence of resistance to oral artemisinin monotherapies. ACTs are produced by combining artemisinin derivatives with complimentary partner drugs, and the net effects of combining these drugs are: (1) rapid action and short period of treatment due to artemisinin derivatives and (2) prevention of recrudescence due to the partner drug [71, 89, 90]. It is against this background that WHO recommended the use of ACTs in the early 2000s in countries that had prevalence of *Plasmodium falciparum* strains that were highly resistant to the conventional available antimalarials [85, 91]. To date, ACTs continue to be among the most effective globally and remain a highly acclaimed first-line treatment for all cases of basic malaria [92]. The recommended ACTs include artemether/lumefantrine and dihydroartemisinin/piperaquine [93]. The efficacy of the artemisinins has been reported to be based on their activity, which have been improved by utilized synthetic artemisinin dimers, trimers, as well as tetramers without interfering with the peroxide bridge [94]. Generally, improving ACTs activity improves efficacy and postpone the development of resistance to malarial parasites. Although ACTs have been characterized with high curative activity, reports of *P. falciparum* strains with elevated resistance to ACTs have been presented in the Greater Mekong Region [95]. Faced with resistance against ACTs, some regions have adopted triple artemisinin-based combination therapy (TACT against multidrug resistant *P. falciparum* while awaiting registration of novel antimalarial drugs [96]. The efficacy of TACT is based on molecular antimalarial resistance mechanisms, which indicate counter-selection of antimalarial resistance by frequently utilized drugs, (1) piperaquine and (2) mefloquine [93].
