Plasmodium falciparum: multifaceted resistance to artemisinins

Malaria Journal

Table 1 Date of introduction and first reports of anti-malarial drug resistance, resistance genes involved [33, 86, 87] and main mechanisms of resistance

Anti-malarial drug	Introduced	First reported resistance	Resistance genes	Main resistance mechanisms Refs
Quinine	1632	1910	Pfmdr1/other	Disruption of drug accumulation inside the food vacuole by reduced propensity of the drug transporter PfMDR1 to bind to and transfer the anti-malarial	[88, 89]
Chloroquine	1945	1957	Pfcrt/Pfmdr1	Drug extrusion on from digestive vacuole by mutated drug transporter PfCRT due to higher lipophilicity and negativity of the transporter allowing ionized chloroquine efflux	[90–92]
Proguanil	1948	1949	Pfdhfr	Modification of the drug target: reduced inhibition of enzymatic activity by the drug	[9]
Sulfadoxine-pyrimethamine	1967	1967	Pfdhps-Pfdhfr		[9]
Mefloquine	1977	1982	Pfmdr1/other	Reduction of parasite susceptibility to mefloquine by amplification of Pfmdr1 copy number	[93]
Atovaquone	1996	1996	Pfcytb	Modification of the drug target by disruption of Cytochrome bc1 complex	[8]
Artemisinins	1980s	2006	Pfk13	Quiescence	[31, 33]

ISSN: 1475-2875