# An MRI Ancillary Study of Malaria Fever Control RCT

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $282,665

## Abstract

Contact PD/PI: BIRBECK, GRETCHEN L.
ABSTRACT
Despite eradication efforts, ~400,000 African children sustained brain injuries as a result of CNS malaria in
2016. A higher maximum temperature (Tmax) during the acute malaria infection is an established risk factor for
neurologic sequelae and a randomized controlled trial (RCT) of aggressive antipyretic therapy with
acetaminophen and ibuprofen began enrollment in Malawi in 2019 (R01NS102176) with expansion into
Zambia pending. In this clinical trial, the primary outcome is Tmax during the acute infection. However, the
antipyretic therapies used in this RCT may offer neuroprotective benefits without affecting Tmax--for example,
neuroprotection through anti-inflammatory mechanisms. In this ancillary study, we propose to use
neuroimaging in the context of the RCT to further evaluate the potential neuroprotective effects of aggressive
antipyretic therapy for CNS malaria and explore possible mechanisms for these effects. Comparing children
allocated to aggressive antipyretic therapy vs. usual care on the prevalence of structural brain abnormalities
after recovery from CNS malaria will facilitate the evaluation of non-fever pathways for neuroprotection. Both
Zambia and Malawi have an unusually well developed infrastructure for advanced imaging in the academic
Brain MRIs will be obtained in
children enrolled in the RCT at 1- and 12-months post recovery. Analyses will be completed comparing the
odds of having any structural injury based upon RCT treatment allocation and based upon (Tmax) stratified by
treatment allocation to assess changes specifically related to response to therapy in terms of fever reduction.
Potential mechanisms of aggressive antipyretic-related injury will be evaluated including assessments for
treatment-related CNS bleeds. Neuroimaging is a well-established, valid proxy for neurological outcomes after
brain injury including in pediatric CNS malaria. Adding this MRI ancillary study to our fever RCT may elucidate
mechanisms of treatment-associated injury and allow for early identification of neuroprotection from aggressive
antipyretic use that would otherwise require long-term follow-up for cognitive and behavioral assessments. This
MRI ancillary study when added to the Fever RCT will provide critical insights that could inform future
neuroprotective studies of malaria that might incorporate imaging to optimize study design.
centers where the RCT using aggressive antipyretic therapy will be conducted.
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Project Summary/Abstract

## Key facts

- **NIH application ID:** 10117293
- **Project number:** 5R01NS111057-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** GRETCHEN L. BIRBECK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $282,665
- **Award type:** 5
- **Project period:** 2020-03-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117293

## Citation

> US National Institutes of Health, RePORTER application 10117293, An MRI Ancillary Study of Malaria Fever Control RCT (5R01NS111057-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10117293. Licensed CC0.

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