Abstract
BackgroundSingle nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes.Methodology/Principal FindingsSamples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA–based quantitative nucleic acid sequence–based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up.Conclusions/SignificanceIn our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites.
Highlights
Artemisinin-based combination therapy (ACT) is widely advocated as first-line antimalarial treatment
The relation between mutations in dhfr, enrolment parasitemia, parasite clearance and post-treatment gametocyte carriage was determined in baseline samples from 134 individuals treated with SP or SP+AQ and 57 individuals treated with SP+AS (ACT)
Transmission potential during follow-up was quantified as the area under the curve (AUC) of Pfs25 QT-NASBA gametocyte density versus time for non-ACT and ACT treated children
Summary
Artemisinin-based combination therapy (ACT) is widely advocated as first-line antimalarial treatment. Drugs that are no longer recommended as first-line treatment, such as sulphadoxine-pyrimethamine (SP), will continue to play a role in malaria control. SP plays an important role in intermittent preventive treatment to control malaria in infants [3,4] and pregnant women [5] and in some situations the combination of SP with amodiaquine (AQ) may be a cheap and efficacious alternative to ACT [6,7]. Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxinepyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. We determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes
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