Creating and Validating Ligase Primers to Detect Single Nucleotide Polymorphisms Associated with Atovaquone Resistance in Plasmodium falciparum

Atovaquone-proguanil is one of the most commonly prescribed malaria prophylactic drugs. However, sporadic mutations conferring resistance to atovaquone have been detected in recent years associated with single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum cytochrome b ( pfcytb) gene....

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Bibliographic Details
Published in:The American journal of tropical medicine and hygiene 2023-04, Vol.108 (4), p.777-782
Main Authors: Alruwaili, Muharib, Elahi, Rubayet, van Schalkwyk, Donelly, Sutherland, Colin, Shapiro, Theresa, Prigge, Sean, Sullivan, David
Format: Article
Language:English
Subjects:
Antimalarials - therapeutic use
Atovaquone - therapeutic use
Cytochromes b - genetics
DNA Primers
Drug Combinations
Drug resistance
Drug Resistance - genetics
Humans
Ligases - genetics
Malaria
Malaria, Falciparum - drug therapy
Plasmodium falciparum - genetics
Polymorphism, Single Nucleotide
Proguanil - therapeutic use
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Summary:Atovaquone-proguanil is one of the most commonly prescribed malaria prophylactic drugs. However, sporadic mutations conferring resistance to atovaquone have been detected in recent years associated with single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum cytochrome b ( pfcytb) gene. Monitoring polymorphisms linked with resistance is essential in assessing the prevalence of drug resistance and may help in designing strategies for malaria control. Several approaches have been used to study genetic polymorphisms associated with antimalarial drug resistance. However, they either lack high throughput capacity or are expensive in time or money. Ligase detection reaction fluorescent microsphere assay (LDR-FMA) provides a high-throughput method to detect genetic polymorphisms in P. falciparum. In this study, we have created primers to detect SNPs associated with clinically relevant atovaquone resistance using LDR-FMA and validated them in clinical samples. Four SNPs from pfcytb gene were analyzed using LDR-FMA. The results were 100% consistent with DNA sequence data, indicating that this method has potential as a tool to detect genetic polymorphisms associated with atovaquone resistance in P. falciparum.
ISSN:0002-9637
1476-1645
DOI:10.4269/ajtmh.22-0700