# Defining the mechanism of coma in cerebral malaria

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2024 · $527,997

## Abstract

ABSTRACT
Malaria remains a significant public health challenge that has resisted worldwide control efforts. Some individuals
who become infected with Plasmodium falciparum develop cerebral malaria (CM), which presents as a coma
and is associated with high morbidity and mortality. The etiology of CM coma, which is reversible in survivors,
remains unknown. We have identified high blood levels of pipecolic acid (PA) in children with CM compared to
mild malaria. PA has been shown to induce coma in animal models, and we will test the hypothesis that high
blood levels in CM result in abnormally elevated PA central nervous system (CNS) concentrations to result coma
in CM. We will determine if PA cerebral spinal fluids are elevated in CM compared with defined non-CM cases
of encephalopathy. We will determine if PA is enriched in the brain of mice in infected with P. berghei ANKA in
the experimental cerebral malaria model and not in the brains of mice infected with strains P. yoelii and P.
chabaudi, which are infection models where mice maintain wakefulness. We will investigate the hypothesis that
PA reduces consciousness through γ-aminobutyric acid (GABA) receptors, which has been suggested by prior
studies using a rat model. PA has been shown by multiple groups including ours to be produced by Plasmodium,
and its role in parasite biology is unknown. We will define the metabolic pathway that produces PA and test
whether PA protects the malaria parasite from oxidative stress, similar to its protective role observed in
mammalian cells. Overall, our goals are to define the role of PA in coma induction and parasite biology to
characterize a novel mechanism of coma in humans, potentially identify a biomarker of CM etiology of coma,
and characterize a potential novel target for improving the health outcomes of CM.

## Key facts

- **NIH application ID:** 10848352
- **Project number:** 5R01AI164864-03
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Johanna Patricia Daily
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $527,997
- **Award type:** 5
- **Project period:** 2022-07-08 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848352

## Citation

> US National Institutes of Health, RePORTER application 10848352, Defining the mechanism of coma in cerebral malaria (5R01AI164864-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10848352. Licensed CC0.

---

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