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  • Title: Selection of Cytochrome b Mutants Is Rare among Plasmodium falciparum Patients Failing Treatment with Atovaquone-Proguanil in Cambodia.
    Author: Lin JT, Waltmann A, Moser KA, Park Z, Na YB, Aydemir O, Brazeau NF, Gosi P, Marsh PW, Muller MS, Spring M, Sok S, Bailey JA, Saunders DL, Lon C, Wojnarski M.
    Journal: Antimicrob Agents Chemother; 2021 Feb 17; 65(3):. PubMed ID: 33361308.
    Abstract:
    Atovaquone-proguanil remains effective against multidrug-resistant Plasmodium falciparum in Southeast Asia, but resistance is mediated by a single point mutation in cytochrome b (cytb) that can arise during treatment. Among 14 atovaquone-proguanil treatment failures in a clinical trial in Cambodia, only one recrudescence harbored the cytb mutation Y268C. Deep sequencing did not detect the mutation at baseline or in the first 3 days of treatment, suggesting that it arose de novo Further sequencing across cytb similarly found no low-frequency cytb mutations that were up-selected from baseline to recrudescence. Copy number amplification in dihydroorotate dehydrogenase (DHODH) and cytb as markers of atovaquone tolerance was also absent. Cytb mutation played a minor role in atovaquone-proguanil treatment failures in an active comparator clinical trial.
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