# Optimal chemopreventive regimens to prevent malaria and improve birth outcomes in Uganda

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $1,194,675

## Abstract

PROJECT SUMMARY/ABSTRACT
Malaria in pregnancy remains a major challenge in Africa, where approximately 50 million women are at risk for
P. falciparum infection during pregnancy each year. Among pregnant women living in malaria endemic areas
symptomatic disease is uncommon, but infection with malaria parasites is associated with maternal anemia
and adverse birth outcomes including abortions, stillbirth, preterm birth, low birth weight (LBW), and infant
mortality. The World Health Organization (WHO) recommends the use of long-lasting insecticidal nets (LLINs)
and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for the prevention of malaria in
pregnancy in endemic areas of Africa. However, there is concern for diminishing efficacy of these interventions
due to the spread of vector resistance to the pyrethroid insecticides used in LLINs and parasite resistance to
SP. Thus, there is an urgent need for new strategies for the prevention of malaria in pregnancy and improving
birth outcomes. Artemisinin-based combination therapies (ACTs) are now the standard treatment for malaria in
Africa. Dihydroartemisin-piperaquine (DP) is a fixed-dose ACT and an attractive alternative to SP for IPTp. DP
is highly efficacious, and the long half-life of piperaquine provides at least 4 weeks of post-treatment
prophylaxis. Recent randomized controlled trials from our group and others showed that, compared to IPTp
with SP, IPTp with DP dramatically reduced risks of malaria-specific outcomes but there were minimal
differences between the SP and DP groups in risks of adverse birth outcomes. The key question motivating
this proposal is why IPTp with either SP or DP is associated with similar risks of adverse birth outcomes
despite the far superior antimalarial activity of DP. The likely explanation is that SP, a broad-spectrum
antibiotic, protects against non-malarial causes of LBW and preterm birth. Our central hypothesis is that SP
improves birth outcomes independent of its antimalarial activity and that IPTp with a combination of SP+DP will
offer antimalarial and non-antimalarial benefits, thus providing superior prevention of adverse birth outcomes
compared to either drug used alone. To test this hypothesis we will conduct a double-blinded randomized
clinical trial in a rural area of Uganda with very high malaria transmission intensity, where our group already
has an established infrastructure for clinical research. Our specific aims will be (1) to compare the risk of
adverse birth outcomes among pregnant women randomized to receive monthly IPTp with SP vs. DP vs.
SP+DP, (2) To compare safety and tolerability of IPTp regimens among pregnant women randomized to
receive monthly IPTp with SP vs. DP vs. SP+DP, and (3) to compare risks of malaria-specific and non-malarial
outcomes among pregnant women randomized to receive monthly IPTp with SP vs. DP vs. SP+DP. This study
will be the first to evaluate the efficacy and safety of a novel combination o...

## Key facts

- **NIH application ID:** 9849908
- **Project number:** 1U01AI141308-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MATTHEW G DORSEY
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,194,675
- **Award type:** 1
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849908

## Citation

> US National Institutes of Health, RePORTER application 9849908, Optimal chemopreventive regimens to prevent malaria and improve birth outcomes in Uganda (1U01AI141308-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9849908. Licensed CC0.

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