Emergence of resistance to atovaquone-proguanil in malaria parasites: insights from computational modeling and clinical case reports.

ABSTRACT: The usefulness of atovaquone-proguanil (AP) as an antimalarial treatment is compromised by the emergence of atovaquone resistance during therapy. However, the origin of the parasite mitochondrial DNA (mtDNA) mutation conferring atovaquone resistance remains elusive. Here, we report a patient-based stochastic model that tracks the intrahost emergence of mutations in the multicopy mtDNA during the first erythrocytic parasite cycles leading to the malaria febrile episode. The effect of mtDNA copy number, mutation rate, mutation cost, and total parasite load on the mutant parasite load per patient was evaluated. Computer simulations showed that almost any infected patient carried, after four to seven erythrocytic cycles, de novo mutant parasites at low frequency, with varied frequencies of par

SUBMITTER: Cottrell G 

PROVIDER: S-EPMC4136057 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature