Plasmodium falciparum infection dynamics and transmission potential following treatment with sulfadoxine-pyrimethamine.
OBJECTIVE
To investigate the overall efficacy of sulfadoxine-pyrimethamine (SP) treatment and the corresponding transmission potential for patients infected with SP-resistant Plasmodium falciparum.


METHODS
A mathematical model of the in-host dynamics of P. falciparum infections was used to simulate infections with parasites having different numbers of mutations in the dhfr and dhps genes and their responses to SP treatment. The treatment outcome and transmission potential of each simulated infection following SP treatment was assessed by tracking asexual parasite density and the number of days with sufficient mature gametocytes to give a > 95% probability of infecting a mosquito.


RESULTS
The results show treatment failure only occurring in patients infected with parasites having two mutations in dihydrofolate reductase (DHFR) combined with at least two mutations in dihydropteroate synthetase (DHPS) or with parasites having a triple mutation in DHFR. Highly mutated parasites (three mutations in each gene) caused the highest clinical failure rate, while moderately mutated parasites (three mutations in DHFR plus one mutation in DHPS) produced a high rate of asymptomatic parasitological failure following SP treatment. This high rate of asymptomatic recrudescence caused the transmission potential of infections with moderately resistant parasites to exceed that of highly resistant parasites.


CONCLUSIONS
The model output suggests that infection dynamics following SP treatment and the overall transmission potential are inherently linked. The combination of prolonged asymptomatic parasitaemia and increased transmission potential allows parasites having three mutations in DHFR, but fewer mutations in DHPS, to expand largely unnoticed.
Gatton
Michelle L
ML
Australian Centre for International and Tropical Health and Nutrition, University of Queensland Brisbane, Australia. michelle.gatton@qimr.edu.au
Cheng
Qin
Q
D000465:Algorithms; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000635:transmission*; D008954:Models, Biological; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*
D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine