# Elucidating mechanisms for artemisinin-induced dormancy in Plasmodium falciparum

> **NIH NIH R21** · UNIVERSITY OF GEORGIA · 2023 · $226,500

## Abstract

Project Summary
Among the numerous problems plaguing the malaria elimination efforts is the emergence and spread of
drug resistance in P. falciparum. Resistance to artemisinin has led to reduced efficacy of artemisinin
combination therapy (ACTs) and ultimately selection of resistance to the partner drugs (e.g., piperaquine).
Clearly the threat of multi-drug resistant malaria is as important today as it has ever been, with the precious
gains in malaria control threatened by the potential for the spread of P. falciparum strains that are resistant
to all currently available treatment drugs. Resistance to artemisinin is not the only factor responsible for
treatment failures. Even before artemisinin resistance emerged, recrudescent infections were commonly
observed when patients were treated with artemisinin derivatives alone. In some studies, even 5-7 days of
treatment with artesunate alone led to ~10% recrudescent infections. The underlying cause of these
recrudescent infections has been attributed to the unique ability of artemisinin to arrest the growth of ring
stages of P. falciparum. These dormant rings can persist for days to weeks before recovering and growing
normally to cause a recrudescent infection. Our published and preliminary data led us to the hypothesis
that selection of artemisinin resistance is a two-step process in which the initial responses of the parasite
to artemisinin drug pressure is an enhanced dormancy phenotype that confers increased tolerance to drug;
subsequently resistance conferring mutations occur (e.g., K13). In Aim 1 we will overexpress genes in a
novel chromosome 10 copy number variant we identified in independently derived artemisinin-resistant
clones. In Aim 2 will use novel high content imaging assays to quantify enhanced dormancy recovery
phenotypes in artemisinin-resistant versus -susceptible P. falciparum. The results of these studies will
provide evidence for the molecular basis of recovery from artemisinin-induced dormancy and possibly
reveal new mechanisms of resistance to artemisinin.

## Key facts

- **NIH application ID:** 10742385
- **Project number:** 1R21AI168803-01A1
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** DENNIS E KYLE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $226,500
- **Award type:** 1
- **Project period:** 2023-08-16 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10742385

## Citation

> US National Institutes of Health, RePORTER application 10742385, Elucidating mechanisms for artemisinin-induced dormancy in Plasmodium falciparum (1R21AI168803-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10742385. Licensed CC0.

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