ArticleMalaria journal2017
Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection.
Article in Malaria journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors at 2 institutions in 2 countries.
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Abstract
backgroundTo study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone and pyrimethamine in Plasmodium yoelii was examined in such a model.
methodsTreatment of P. yoelii infected mice, with atovaquone or pyrimethamine, was started at parasitaemia level of 3-5%, interrupted when reduced to less than 0.4%, and restarted following parasitaemia recovery to the initial level. Treatment cycles were repeated until stable phenotype resistance was observed.
resultsPlasmodium yoelii rapidly developed resistance to atovaquone (2.75 ± 1.06 cycles) and to pyrimethamine (5.4 ± 0.89 cycles) under RIT. A dose dependent phenomenon in the selection of atovaquone resistance mutations was observed. All mutations that underlie resistance to therapeutic doses of 0.3-1.44 mg kg
conclusionsRIT of P. yoelii infected mice led to rapid development of resistance to atovaquone and pyrimethamine. The dose dependent selection of resistance mutants to atovaquone observed during RIT might reflect the outcome of two different causes of malaria treatment failure in human, repeated incomplete treatment with therapeutic dose and repeated inadequate treatment associated with sub-therapeutic dose, and need to be systematically investigated.
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