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  • dhfr and dhps mutations supporting their role in SP drug resistance and/or treatment failure.
dhfr and dhps mutations supporting their role in SP drug resistance and/or treatment failure.
Abdul-Ghani R, Farag HF, Allam AF. Sulfadoxine-pyrimethamine resistance in Plasmodium falciparum: a zoomed image at the molecular level within a geographic context. Acta Trop. 2013 125(2):163-90. Review. PMID:23131424
Summary of some previous studies on dhfr and dhps mutations supporting their role in SP drug resistance and/or treatment failure.
Country Mutations in dhfr Mutations in dhps Notes PMID
Papua New Guinea C59R, S108N/T – Correlation between in vitro susceptibility to pyrimethamine and cycloguanil and S108N or C59R/S108N 8780462
Kenya N51I, C59R, S108N Not studied Significant association of S108N with in vitro pyrimethamine resistance 9449279
N51I, C59R, S108N A437G, K540E The dhfr triple and dhps double mutants indicates more risk of SP treatment failure 15642957
N51I, C59R, S108N A437G, K540E Association of the quintuple dhfr/dhps mutant with SP treatment failure in patients with severe falciparum malaria 11784419
N51I, C59R, S108N S436A, A437G, K540E Association of more than two dhfr mutations with or without any dhps mutation with SP treatment failure in an endemic area Association of combined S108N and A437G or of A437G alone with SP treatment failure in an epidemic area 11491006
Gabon N51I, C59R, S108N A437G, K540E Association of dhfr and dhps mutations to SP treatment failure 10471565
N51I, C59R, S108N S436A, C, K540E Association of high rates of the triple dhfr mutant and A437Gand emergence of K540E with SP treatment failure among children 21569596
Cameroon N51I, C59R, S108N S436A, A437G, K540E The dhfr triple mutant may be associated with adequate clinical response or early treatment failure 10813484
Colombia N51I, S108N A437G Delayed parasite clearance associated with N51I, S108N that may contribute to the spread of drug resistance 12142257
Malawi N51I, C59R, S108N A437G, K540E Strong correlation between SP treatment failure and the dhfrtriple and dhps double mutants 11807721
Tanzania N51I, C59R, S108N, I164L Not studied Association of these mutations with the firstly reported I164L in African isolates with SP treatment failure 12630380
N51I, C59R, S108N A437G, K540E Association of this quintuple mutant with in vivo resistance 15642957
N51I, C59R, S108N A437G, K540E, A581G Possible association of the dhps triple mutant with early SP treatment failure 19238219
Uganda N51I, C59R, S108N A437G, K540E Predictability of mutations as markers for SP treatment failure is related to age 15117308
N51I, C59R, S108N A437G, K540E Association of the quintuple mutant to SP treatment failure with C59R and A437G being the most predictive 14628939
Laos N51I, C59R, S108N S436A, A437G,  K540E, A581G Correlation between in vivo SP resistance and mutations (particularly, S108N and A437G) 12950663
India C59R, S108N S436A, A581G,  A613T Association between in vitro pyrimethamine and sulfadoxine resistance and mutations in dhfr and dhps, respectively 15047993
Ghana N51I, C59R, S108N A437G, K540E Association of the dhfr triple mutant only to SP treatment failure, prolonged parasite clearance and increased gametocyte carriage 16135198
Nigeria N51I, C59R, S108N A437G, K540E Independent association of the quintuple mutant to SP treatment failure in all age groups of children and of triple or double mutants with failure in children <5 years; association of less than two mutations with treatment success 16023986
Mozambique N51I, C59R, S108N A437G, K540E Association of dhfr triple and dhfr/dhps quintuple mutants to SP treatment failure 7 days after treatment among Mozambican children in Maputo 17876469
Congo N51I, C59R, S108N S436A, A437G Association of C59R, A437G and the quadruple mutant N51I, C59R, S108N/A437G with recrudescence 17956498
Northeast India N51Y, C59R, S108N, I164L D404E, V453L, A581G 25184337
S436A, K540E
K540E, A581G
D404E, S436A, K540E
D404E, K540E, A581G,
S436A. V498L, K540E
S436A, V453L, V498L, K540E
Summary of some previous studies on dhfr and dhps mutations supporting their role in SP drug resistance and/or treatment failure.
Country Mutations in dhfr Mutations in dhps Notes PMID
Gabon N51I, C59R, S108N S436A, A437G No sufficient correlation between in vivo treatment failure and both in vitro resistance and molecular markers 12805261
Papua New Guinea C59R, S108N Not observed These two mutations may not be sufficient for treatment failure but indicate the potential of resistance evolution 15031512
Tanzania N51I, C59R, S108N S436A, A437G,  K540E No association between pre-treatment mutations in dhfr and dhps and in vivo SP resistance 9735930
N51I, C59R, S108N A437G, K540E No relationship between dhfr and dhps genotypes and in vivoclinical outcomes in under-five rural children prior to adoption of SP as first-line treatment 15099990
N51I, C59R, S108N A437G, K540E No relationship between dhfr and dhps genotypes and in vivoclinical outcomes in under-five rural children 3 years after adoption of SP as first-line treatment 18082233
Uganda N51I, C59R, S108N S436A, A437G No correlation between the clinical outcome of SP treatment and high frequencies of these mutations 15941416
Cameroon N51I, C59R, S108N A437G No association between the clinical outcome of SP treatment and the presence of quadruple or triple mutants 17640607
N51I, C59R, S108N A437G No correlation between the clinical outcome of SP treatment and mutations Mbacham et al. (2009)
Iran N51I, C59R, S108N, I164L S436A, A437G, A581G No correlation between in vivo resistance and the quintuple mutant, but A437G shows correlation 17024359
Kenya N51I, C59R, S108N, I164L Not studied No association between I164L within quadruple or triplemutants and SP treatment failure in adults
18321547
Online articles related to dhfr and dhps mutations supporting their role in SP drug resistance and/or treatment failure. retrieved from PubMed

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