# Pharmacological insights into antimalarial exposure, clinical outcomes, and drug resistance in Africa

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $727,306

## Abstract

Project Summary
Malaria remains an enormous problem, and drugs are of critical importance to treat episodes of malaria,
prevent disease in high risk groups, and limit transmission. Artemisinin-based combination therapies (ACTs),
mostly artemether-lumefantrine or artesunate-amodiaquine, are the cornerstones of antimalarial therapy in
Africa. Standard chemoprevention approaches are intermittent preventive therapy with sulfadoxine-
pyrimethamine (SP) in pregnant women and seasonal malaria chemoprevention with amodiaquine+SP in
children in the Sahel sub-region, and improved approaches are under study. In this context, antimalarial drug
resistance is of great concern. Resistance to ACTs, including both artemisinins and partner drugs, has
emerged in southeast Asia. Resistance to amodiaquine and SP is longstanding, but sensitivities vary, with
uncertain impacts on chemoprevention. Definitive studies in at risk populations of associations between
exposure to antimalarial drugs, treatment and preventive efficacy, and selection of drug resistance are needed.
This project will build on studies in Uganda during our first cycle of funding in which we characterized the
pharmacokinetics (PK) and pharmacodynamics of the ACT dihydroartemisinin-piperaquine, the most promising
new agent for chemoprevention in Africa. Our goals will be broadened to gain insights into associations
between drug exposure, malaria outcomes, birth outcomes, and selection of drug resistance in the context of
the 3 primary indications for antimalarial drugs in Africa: treatment of malaria, chemoprevention in pregnancy,
and chemoprevention in children exposed to seasonal malaria. A guiding principal is that the best means of
preventing selection of drug resistance is to effectively treat and prevent malaria, as inadequate exposure to
antimalarial drugs increases risks for both drug sensitive and drug resistant malaria. Our studies will build on
our pharmacology expertise and longstanding collaborations between UCSF and malaria research groups in
Uganda and Burkina Faso. We will use rigorous PK assessments to test related hypotheses in children in
Uganda and Burkina Faso and pregnant women in Uganda that exposure to ACTs is associated with risks of
malaria and the selection of drug-resistant parasites. Better characterization of associations between drug
exposure and clinical and drug resistance outcomes will help us to optimize use of drugs for the treatment and
prevention of malaria. Specific aims will be: 1) to characterize associations between exposure to key ACT
partner drugs, clinical outcomes, and selection of drug resistance in Ugandan children treated for malaria, 2) to
evaluate associations between exposure to DP and SP and protection against malaria and adverse birth
outcomes in pregnant Ugandan women, and 3) to characterize associations between exposure to seasonal
malaria chemoprevention drugs and malaria outcomes in children in Burkina Faso. These studies will help to
identify ...

## Key facts

- **NIH application ID:** 10165467
- **Project number:** 5R01AI117001-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** FRANCESCA T. AWEEKA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $727,306
- **Award type:** 5
- **Project period:** 2015-02-10 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165467

## Citation

> US National Institutes of Health, RePORTER application 10165467, Pharmacological insights into antimalarial exposure, clinical outcomes, and drug resistance in Africa (5R01AI117001-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10165467. Licensed CC0.

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