Michelle L Gatton1, Qin Cheng. 1. Australian Centre for International and Tropical Health and Nutrition, University of Queensland Brisbane, Australia. michelle.gatton@qimr.edu.au
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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.
Authors: James G Kublin; Fraction K Dzinjalamala; Deborah D Kamwendo; Elissa M Malkin; Joseph F Cortese; Lisa M Martino; Rabia A G Mukadam; Stephen J Rogerson; Andres G Lescano; Malcolm E Molyneux; Peter A Winstanley; Phillips Chimpeni; Terrie E Taylor; Christopher V Plowe Journal: J Infect Dis Date: 2002-01-17 Impact factor: 5.226
Authors: C H Sibley; J E Hyde; P F Sims; C V Plowe; J G Kublin; E K Mberu; A F Cowman; P A Winstanley; W M Watkins; A M Nzila Journal: Trends Parasitol Date: 2001-12
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Authors: M Eichner; H H Diebner; L Molineaux; W E Collins; G M Jeffery; K Dietz Journal: Trans R Soc Trop Med Hyg Date: 2001 Sep-Oct Impact factor: 2.184
Authors: H S Nagesha; G J Casey; A I Susanti; D J Fryauff; J C Reeder; A F Cowman Journal: Trans R Soc Trop Med Hyg Date: 2001 Jan-Feb Impact factor: 2.184