# Project-003

> **NIH NIH U19** · UNIVERSITY OF SOUTH FLORIDA · 2023 · $365,771

## Abstract

PROJECT SUMMARY
Multidrug-resistant (MDR) Plasmodium falciparum is largely responsible for the global resurgence of malaria. 
Artemisinin-based combination therapies (ACTs) are the most effective frontline treatments for Plasmodium 
falciparum malaria. Therefore, the recent emergence and spread of artemisinin resistance in the Greater 
Mekong Subregion of Southeast Asia, the epicenter of MDR P. falciparum, has raised global concerns. More 
worrisome, clinical resistance to dihydroartemisinin-piperaquine (DHA/PPQ) also has been detected recently in 
this region. Since DHA/PPQ is being considered for use in mass drug administration programs or for seasonal 
malarial prophylaxis in African settings, it is hence important to characterize the clinical phenotype of 
DHA/PPQ resistance and identify molecular markers of resistance to this drug. Artemisinin resistance, 
manifested as delayed parasite clearance following treatment with artemisinins, is associated with mutations in 
the K13 gene, but the molecular mechanism of K13-mediated artemisinin resistance remains to be elucidated. 
Moreover, the molecular mechanism of resistance to the partner drug piperaquine is not understood. To 
address this urgent problem, we will use a combination of molecular and population genomic approaches to 
investigate the mechanisms of antimalarial drug resistance and monitor the evolution and spread of resistant 
parasites. In this project, we propose to (1) identify molecular markers associated with piperaquine resistance, 
(2) determine the mechanisms of K13-mediated artemisinin resistance, and (3) longitudinally track the 
emergence and spread of artemisinin and piperaquine resistance in the strategically selected sentinel sites of 
the Greater Mekong Subregion. Results from this project will be highly useful for effectively monitoring, curbing 
and deterring the evolution of resistance to ACTs, and will provide guidance to malaria chemotherapy in and 
beyond this region.

## Key facts

- **NIH application ID:** 10821532
- **Project number:** 5U19AI089672-15
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** LIWANG CUI
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $365,771
- **Award type:** 5
- **Project period:** 2010-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821532

## Citation

> US National Institutes of Health, RePORTER application 10821532, Project-003 (5U19AI089672-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10821532. Licensed CC0.

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