# Mechanisms of anemia in malaria

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $254,250

## Abstract

Summary
Anemia frequently accompanies infections, contributing to adverse outcomes and even death. The mechanisms
underlying this complication in different infections appear to be diverse and are, in general, not well-defined.
The major infectious disease contributing globally to pediatric anemia is malaria, which is responsible for the
majority of anemia-related hospital admissions in endemic areas and is a major cause of death in children.
Although malaria is caused by Plasmodium infection of red blood cells (RBC), the main contributing factor to
malarial anemia is the loss of uninfected RBC through still largely uncharacterized mechanisms. Therefore, there
is a great need for a better understanding of the mechanisms causing malarial anemia that could lead to targeted
treatments for this severe complication.
We have recently analyzed plasma samples from a cohort of 552 Ugandan children with severe malaria to study
the role of Xanthine Oxidase (XO), an oxidative enzyme that is upregulated in the plasma of malaria patients.
We have observed a strong association between the levels of XO in plasma and the development of severe
malarial anemia in children. Additionally, the levels of XO correlated significantly with biomarkers of hemolysis,
suggesting that XO activity may contribute to the loss of uninfected RBC during malaria.
In this project, we intend to determine whether there is a causal relation between the increased levels of XO and
development of severe malarial anemia by studying the mechanisms underlying XO-induced hemolysis and/or
phagocytosis of uninfected RBC in human cells in vitro and in mice models of malaria.
In the first aim we will determine the mechanism underlying XO-induced loss of RBC in vitro. We will study the
effects of XO from patient plasma on healthy human RBC (or RBC co-cultured with Plasmodium falciparum in
vitro) to determine whether XO exposure increases susceptibility to hemolysis, eryptosis and/or phagocytosis by
human monocyte/macrophages.
In the second aim we will determine role of XO in malaria-induced anemia in a mouse model of infection that
reproduces the characteristics human severe malarial anemia: low parasitemia and high, transient loss of
uninfected RBC. We will first determine whether ex vivo exposure to XO increases the loss of RBC transferred
into mice. We will also use specific inhibitors of XO to determine whether XO activity is a major contributor to
anemia.
The validation of XO as a contributor to anemia may open new possibilities for much needed adjunctive therapy
in malaria and other infection-induced hemolytic anemias.

## Key facts

- **NIH application ID:** 10869643
- **Project number:** 1R21AI182931-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** ANA RODRIGUEZ
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2024-06-13 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869643

## Citation

> US National Institutes of Health, RePORTER application 10869643, Mechanisms of anemia in malaria (1R21AI182931-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10869643. Licensed CC0.

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