# Treating Brain Swelling in Pediatric Cerebral Malaria

> **NIH NIH U01** · MICHIGAN STATE UNIVERSITY · 2021 · $1,439,907

## Abstract

Cerebral malaria (CM) is defined as an otherwise unexplained coma in a patient with Plasmodium falciparum
parasitemia. The condition is common, primarily affects African children less than five years old, and has a
large public health impact in endemic areas. Most of the 675,000 malaria deaths each year are from CM; the
case fatality rate is 15%, and 30% of survivors have neurological abnormalities at the time of hospital
discharge. The mainstay of treatment is intravenous antimalarial drugs and supportive care. No adjunctive
therapy has previously been proven effective in decreasing the high rates of mortality and morbidity in this
condition. Our long-term goal is to establish feasible therapies that decrease death and disability rates in this
vulnerable population.
We recently determined that severely increased brain volume in children with CM is strongly associated with
death. In survivors, however, brain volumes diminished quickly, without specific treatment. Recognizing that
increased brain volume is now a specific therapeutic target, we will perform a randomized, non-blinded
controlled clinical trial of two adjunctive therapies: hypertonic saline or early intubation with mechanical
ventilation. The first addresses a likely cause of increased brain volume (cytotoxic edema) and the second
addresses the likely cause of death (respiratory arrest). We will randomize Malawian children with CM and
severely increased brain volumes on screening brain MRI (magnetic resonance imaging) to one of three study
arms: usual treatment (elevation of the head of the bed by 30 degrees, antimalarial drugs, and supportive
care); usual treatment plus intravenous hypertonic saline; or usual treatment plus early intubation and
mechanical ventilation. Our primary outcome will be failure of the first treatment to which the child is assigned
or death, whichever comes first. Secondary outcomes include neurological disabilities at hospital discharge
and thereafter. We hypothesize that subjects randomized to one or both of our intervention arms will show
significantly decreased mortality without a rise in neurological morbidity, compared to those randomized to
usual treatment.
Simultaneously with our clinical trial, we will evaluate candidate biomarkers of increased brain volume in
children with CM. If a biomarker shows internal validity for identifying children with CM with high brain
volumes, this will facilitate uptake of our study results into African hospitals where MRI is unavailable.
In summary, the proposed research is significant because the therapies used in our intervention arms target an
important risk factor for death in children with CM. Should either of the proposed interventions prove to be
efficacious, it will be the first time an adjunctive therapy has been shown to decrease death and/or disability
rates in these children. With widespread adoption of a favorable intervention into other centers, the public
health impact of this devastating neurological in...

## Key facts

- **NIH application ID:** 10075206
- **Project number:** 5U01AI126610-05
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Terrie Ellen Taylor
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,439,907
- **Award type:** 5
- **Project period:** 2016-12-12 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075206

## Citation

> US National Institutes of Health, RePORTER application 10075206, Treating Brain Swelling in Pediatric Cerebral Malaria (5U01AI126610-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10075206. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*