TABLE 1.
Known selective effects of antimalarial drugs on resistance loci of P. falciparum of African origind.
| DRUG | Locus | pfmdr1 | pfcrt |
Other
loci |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||
| Codon | 86 | 184 | 1246 | 74 | 75 | 76 | 220 | 271 | ||
|
| ||||||||||
| Wild-type | N | Y | D | M | N | K | A | Q | ||
| chloroquine | Y | F | - | I | E | T | S | E | ||
| amodiaquine | Y | Y | Y | I | E | T | S | E | ||
| lumefantrinea | N | F | D | M | N | K | A | Q | ||
| artemisininsa | N | F | D | M | N | K | A | Q | ||
| pyronaridine | - | - | - | - | - | - | - | - | ||
| piperaquineb | - | - | Y | - | - | T | - | - | ||
| mefloquinec | N | Y | D | - | - | - | - | - | ||
| sulfadoxine | none | none | none | none | none | none | none | none | pfdhps | |
| pyrimethamine | none | none | none | none | none | none | none | none | pfdhfr | |
Dash ( - ) indicates lack of relevant data.
The combination AL selects for these genotypes; available in vivo and in vitro data suggest both drug components may both contribute to this effect.
A single in vitro study published to date suggests piperaquine may select for pfcrt 76T (Muangnoicharoen et al. 2009), but this has not been shown in vivo. A single study provides some evidence for selection for the 1246Y allele of pfmdr1 (Wong et al. 2011).
There are no recorded cases of mefloquine treatment failure in Africa in parasites which exhibited increased pfmdr1 copy number, as has been frequently described from Asia.
Data summarized from the following studies: Humphreys et al. 2007; Sisowath et al. 2007, 2009; Dokmajilar et al. 2006; Duraisingh et al. 1997, 2000; Muangnoicharoen et al. 2009; Wong et al. 2011.