The impact of drug resistance can also be illustrated by the modification of species composition. The genetic mechanisms of drug resistance in P. falciparum are not yet fully understood. Not only is there an almost perfect correlation between the presence of the mutant codon in 108 and in vitro resistance to pyrimethamine, but the level of in vitro resistance increases with the number of mutations. Resistance to cycloguanil has been linked to Ser Thr mutation in codon 108 associated with Ala Val mutation in codon 16. Ser Asn mutation alone at position 108 is not a good marker for cycloguanil resistance.
Sulfadoxine resistance is also related to mutations at specific codons.
Asn Gly mutations in codon 437 is the key mutation associated with sulfadoxine-resistance. For treatment, sulfadoxine is always prescribed with pyrimethamine. The synergistic anti-malarial action of this drug combination is based on the specific inhibition of two successive enzymes in the folate metabolic pathway. Several mutations are, therefore, associated with therapeutic failure of the sulfadoxine-pyrimethamine combination. Three genes have been identified for chloroquine resistance.