Plasmodium falciparum infection dynamics and transmission potential following treatment with sulfadoxine-pyrimethamine

Gatton, Michelle L and Cheng, Qin (2006) Plasmodium falciparum infection dynamics and transmission potential following treatment with sulfadoxine-pyrimethamine. Journal Of Antimicrobial Chemotherapy, 58 1: 47-51. doi:10.1093/jac/dkl158


Author Gatton, Michelle L
Cheng, Qin
Title Plasmodium falciparum infection dynamics and transmission potential following treatment with sulfadoxine-pyrimethamine
Journal name Journal Of Antimicrobial Chemotherapy   Check publisher's open access policy
ISSN 0305-7453
1460-2091
Publication date 2006-07
Sub-type Article (original research)
DOI 10.1093/jac/dkl158
Volume 58
Issue 1
Start page 47
End page 51
Total pages 5
Place of publication Oxford, England
Publisher Oxford Univ Press
Collection year 2006
Language eng
Subject CX
1117 Public Health and Health Services
Formatted 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.
Keyword malaria
drug resistance
mathematical model
Q-Index Code CX

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 09:05:21 EST