Identification of mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum can predict resistance to sulfadoxine-pyrimethamine therapy. The original study was performed in Blantyre, Malawi.
Resistance to pyrimethamine is associated with mutation(s) in DHFR, while resistance to sulfa drugs is associated with mutation(s) in DHPS.
Treatment failure occurred when all 3 of the following were present:
(1) >= 3 DHFR mutations
(2) >= 2 DHPS mutations
(3) >= 5 total DHFR+DHPS mutations
where:
• The presence of 3 DHFR and 2 DHPS mutations was termed the "quintuple" mutant.
Identification of the following 2 mutants correlated with treatment failure in Africa:
(1) Arg-59 in DHFR (cysteine to arginine at codon 59
(2) Glu-540 in DHPS (lysine to glutamine at codon 540)
Other mutants associated with resistance to DHFR:
(1) Asn-108
(2) Ile-51
(3) Val-16
(4) Leu-164
(5) Arg-50
Other mutants associated with resistance to DHPS:
(1) Ala-436
(2) Ala-437
(3) Gly-581
(4) Phe-436
(5) Thr-613
(6) Ser-613
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