# Examining the mechanisms and optimization of malaria chemoprevention strategies to improve birth outcomes in Africa

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $122,904

## Abstract

PROJECT ABSTRACT
 Reducing the global burden of low birthweight (LBW) remains a high priority for the World Health
Organization (WHO). In Africa, malaria in pregnancy contributes to approximately 20% of LBW cases and
affects nearly 12 million pregnancies every year. To curb the risk of malaria and LBW in Africa, the WHO
recommends intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp with SP), a malaria
chemoprevention strategy for pregnant women living in malaria-endemic settings. However, over the past two
decades, widespread parasite resistance to SP has called for an urgent need to identify alternative
antimalarials that could replace SP. While several antimalarials have been studied to date, the most promising
candidate appears to be dihydroartemisinin-piperaquine (DP). Randomized controlled trials from our group and
others have shown DP to be safe in pregnant women and far superior to SP in preventing malaria. Yet, these
studies yield conflicting results on whether DP is superior to SP in preventing LBW. Mediation analyses
conducted by our group confirm that the reason for this paradoxical finding is that SP, an antimalarial with
known antibiotic and anti-inflammatory properties, improves LBW through mechanisms independent of its
antimalarial activity (e.g., potentially through preventing sexually transmitted and reproductive tract infections,
changing the gut or vaginal microbiome, and reducing maternal inflammation). Moreover, upon further
investigation, the benefits of IPTp with either DP or SP appear to be context-specific, largely driven by the
heterogeneity of the ‘non-malarial’ effects of SP between sites. Thus, in order to inform WHO on the optimal
IPTp regimen, which may require a tailored approach for each setting, further evidence is needed to define the
mechanisms driving the non-malarial effects of SP and for whom and where prevention of the malarial and
‘non-malarial’ mechanisms are most relevant. The objectives of this K99/R00 are to: characterize the
mechanisms that mediate the effect of SP and DP on birthweight (Aim 1), assess the extent to which these
mechanisms and other factors are causing heterogeneity between sites (Aim 2), and develop a model to
estimate which antimalarial combination (either DP, SP, or a combination of DP+SP) would be the most
optimal regimen for each unique epidemiological setting (Aim 3). Our research will leverage existing data from
eight clinical trials conducted across ten study sites. The proposal will build on the applicant’s background in
malaria, clinical trials, and epidemiology and include new training in: (1) the potential ‘non-malarial’ targets of
SP affecting maternal and child health, (2) advanced computational statistics, (3) causal inference methods to
target and tailor interventions. The training plan will be guided by an exemplary mentorship team who are
experts in the field of causal inference, statistics, malaria, and maternal and child health. The combined
resea...

## Key facts

- **NIH application ID:** 10890683
- **Project number:** 5K99HD111572-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Michelle Roh
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $122,904
- **Award type:** 5
- **Project period:** 2023-07-19 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890683

## Citation

> US National Institutes of Health, RePORTER application 10890683, Examining the mechanisms and optimization of malaria chemoprevention strategies to improve birth outcomes in Africa (5K99HD111572-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10890683. Licensed CC0.

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