Selection of Cytochrome b Mutants Is Rare among Plasmodium falciparum Patients Failing Treatment with Atovaquone-Proguanil in Cambodia
| Autor: | Yu Bin Na, Ozkan Aydemir, Mariusz Wojnarski, Michele D. Spring, Patrick W Marsh, Zackary Park, Panita Gosi, Andreea Waltmann, David L. Saunders, Chanthap Lon, Somethy Sok, Kara A. Moser, Nicholas F Brazeau, Jessica T. Lin, Meredith S. Muller, Jeffrey A. Bailey |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
0303 health sciences 030306 microbiology Cytochrome b Point mutation 030231 tropical medicine Plasmodium falciparum Biology biology.organism_classification Virology Atovaquone/proguanil Deep sequencing 03 medical and health sciences 0302 clinical medicine Infectious Diseases parasitic diseases Mutation (genetic algorithm) medicine Dihydroorotate dehydrogenase Pharmacology (medical) Atovaquone medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 65 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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