Triple drug combination screening

The first line treatments for uncomplicated Plasmodium falciparum malaria are artemisinin-based combination therapies (ACT), consisting of an artemisinin derivative combined with a longer acting partner drug. However, the spread of P. falciparum isolates with decreased susceptibility to artemisinin and partner drugs presents a significant challenge to current malaria control efforts. To stem the spread of drug resistant parasites, novel chemotherapeutic strategies are being evaluated, including the implementation of triple artemisinin-based combination therapy (TACT). Currently, there is limited knowledge on the pharmacodynamics and pharmacogenetic interactions of proposed TACT drug combinations. As a means to evaluate these interactions, NCGC scientists have established an in vitro high-throughput assays measuring the drug dose-response to three distinct agents. Sixteen different TACT combinations were screened against fifteen parasite lines from Cambodia, with a focus on parasites with differential susceptibilities to piperaquine and artemisinins. Analysis revealed drug-drug interactions unique to specific genetic backgrounds. The assay and analysis platform can be further leveraged to inform drug policy decisions and evaluate next-generation TACTs.

Project details

Drug Resistance
Drug-based Strategies

Jan 2019 — Jan 2022

$427,431

United States