# Enhancing immunity to malaria in young children with effective chemoprevention

> **NIH NIH U01** · STANFORD UNIVERSITY · 2023 · $1,252,084

## Abstract

PROJECT SUMMARY/ABSTRACT
Malaria continues to result in more than 400,000 deaths annually, mainly in young African children. Effective
immunity to malaria develops in endemic populations, but only after many repeated infections. Intermittent
preventive treatment in pregnancy (IPTp) and childhood (IPTc) have emerged as strategies to decrease
childhood morbidity and mortality, but there is concern that preventing malaria exposure early in life will delay
the development of antimalarial immunity. However, data from our group suggests that interventions that
selectively block the blood stage of malaria infection during this critical time may actually enhance antimalarial
immunity. In this proposal, we will test the hypothesis that preventing blood-stage malaria antigenic exposure
in utero and in young children with IPT enhances protective immunity to malaria by limiting malaria-induced
immunoregulatory mechanisms. To test this hypothesis, we will take advantage of a unique opportunity to
study children born to mothers enrolled in a funded clinical trial of different IPTp regimens in an area of eastern
Uganda with very high malaria transmission intensity. In this parent study, 2757 pregnant women will be
randomized to receive IPTp with sulfadoxine-pyrimethamine (SP, the poorly effective, current standard of
care), the highly effective drug dihydroartemisinin-piperaquine (DP), or both SP+DP. We will leverage this
parent study to enroll a birth cohort of 924 children who will be randomized at birth to receive no IPTc, IPTc
with monthly DP to 1 year of age, or IPTc with monthly DP to 2 years of age. Children will be followed up to 4
years of age. This unique study design will allow us to determine whether effective prevention of blood-stage
malaria exposure with DP-based IPT both in pregnancy and in infancy has lasting benefits for young children
compared with the current standard of care. Our specific aims will be (1) to compare the incidence of malaria
from birth up to 4 years of age among children born to mothers randomized to receive monthly IPTp with SP,
DP, or DP+SP, (2) To compare the incidence of malaria from 2 up to 4 years of age among children
randomized to receive no IPTc in infancy, monthly DP for the first year of life, or monthly DP for the first two
years of life, and (3) To determine whether prevention of malaria with effective IPT leads to lower regulatory
responses and enhanced innate and adaptive immune responses. By determining whether effective prevention
of malaria with IPT during pregnancy and infancy leads to long-term, lasting benefits on infant health, this study
could critically inform policy guidelines, including extending the use of IPT to settings where malaria
transmission is year-round. These studies will also significantly improve our understanding of how preventing
malaria early in life affects infant immune development and the acquisition of antimalarial immunity.

## Key facts

- **NIH application ID:** 10683090
- **Project number:** 5U01AI155325-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Prasanna Jagannathan
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,252,084
- **Award type:** 5
- **Project period:** 2021-07-12 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683090

## Citation

> US National Institutes of Health, RePORTER application 10683090, Enhancing immunity to malaria in young children with effective chemoprevention (5U01AI155325-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10683090. Licensed CC0.

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