# Resistance of Malaria Parasites to Artemisinin-Based Combination Therapies in Uganda

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $656,831

## Abstract

Project Summary
The control and eventual elimination of malaria in Africa is seriously challenged by drug resistance, in
particular resistance to new artemisinin-based combination therapy (ACT) regimens. Worrisome signs suggest
that high level resistance to components of ACT is on the way to Africa, a scary prospect, since the bulk of
serious falciparum malaria occurs on this continent. Improved characterization of the extent of resistance and
mechanisms of resistance is of critical importance. We hypothesize that antimalarial drug sensitivity is
changing in Uganda, that resistance to each relevant drug is mediated by specific parasite mutations, that the
rise of resistance will be dampened and obscured by parasite fitness costs, but that continued drug pressure
will allow emergence of highly fit resistant parasites. Preemptive analysis of parasites will be critical to
characterizing resistance mechanisms before the problem is widespread. To test our hypotheses we will
measure the drug sensitivities of parasites freshly isolated from Ugandan patients, including individuals under
varied levels of drug pressure; characterize the genetic profiles of these parasites; and assess the fitness costs
of resistance in both clinical and laboratory settings. We believe that focused evaluations of fresh Ugandan
isolates will best equip us to characterize drug sensitivity and the emergence of high level resistance in Africa,
where the malaria problem is greatest, and where timely characterization of resistance mechanisms can be
most valuable. Our studies will benefit from access to a wealth of clinical studies in Uganda, including trials
studying the treatment and chemoprevention of malaria, surveillance programs collecting samples from sites
around Uganda, and a cohort study following subjects at varied risks of malaria. Our program will also benefit
from our established laboratories for the study of malaria parasites in Uganda. Our specific aims will be: (1) to
longitudinally characterize the ex vivo sensitivity of malaria parasites to ACT components, (2) to characterize
genetic mediators of varied antimalarial drug sensitivity, and (3) to characterize impacts of varied drug
sensitivity on the fitness of malaria parasites. Our overall goal is to better characterize antimalarial drug
sensitivity and resistance determinants before high level resistance becomes widespread, so that monitoring of
these determinants can guide efforts to circumvent the spread of resistance.

## Key facts

- **NIH application ID:** 10687231
- **Project number:** 5R01AI075045-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Philip Jon Rosenthal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $656,831
- **Award type:** 5
- **Project period:** 2008-08-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687231

## Citation

> US National Institutes of Health, RePORTER application 10687231, Resistance of Malaria Parasites to Artemisinin-Based Combination Therapies in Uganda (5R01AI075045-14). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10687231. Licensed CC0.

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