Methylene blue treatment of fatal cerebral malaria and identification of potential blood biomarkers

Jing Wen Hang, Yew Wai Leong, Vipin Narang, Piyanate Sunyakumthorn, Rawiwan Im-Erbsin, Shihui Foo, Josephine Lum, Bernett Lee, Arthur E. Brown, Laurent Rénia, Gareth D. H. Turner, Samuel C. Wassmer, Eric D. Lombardini, Bruce Russell and Benoît Malleret ()
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Jing Wen Hang: National University of Singapore, Department of Microbiology and Immunology, Immunology Translational Research Programme, Yong Loo Lin School of Medicine
Yew Wai Leong: National University of Singapore, Department of Microbiology and Immunology, Immunology Translational Research Programme, Yong Loo Lin School of Medicine
Vipin Narang: Technology and Research (A*STAR), Singapore Immunology Network (SIgN), Agency for Science
Piyanate Sunyakumthorn: Armed Forces Research Institute of Medical Sciences (AFRIMS), Department of Veterinary Medicine
Rawiwan Im-Erbsin: Armed Forces Research Institute of Medical Sciences (AFRIMS), Department of Veterinary Medicine
Shihui Foo: Technology and Research (A*STAR), Singapore Immunology Network (SIgN), Agency for Science
Josephine Lum: Technology and Research (A*STAR), Singapore Immunology Network (SIgN), Agency for Science
Bernett Lee: Technology and Research (A*STAR), Singapore Immunology Network (SIgN), Agency for Science
Arthur E. Brown: Mahidol University, Faculty of Medical Technology
Laurent Rénia: Technology and Research (A*STAR), A*STAR Infectious Diseases Labs, Agency for Science
Gareth D. H. Turner: Mahidol University, Mahidol Oxford Clinical Research Unit, Faculty of Tropical Medicine
Samuel C. Wassmer: London School of Hygiene & Tropical Medicine, Department of Infection Biology
Eric D. Lombardini: Armed Forces Research Institute of Medical Sciences (AFRIMS), Department of Veterinary Medicine
Bruce Russell: Nagasaki University, Department of Protozoology, Institute of Tropical Medicine (NEKKEN)
Benoît Malleret: National University of Singapore, Department of Microbiology and Immunology, Immunology Translational Research Programme, Yong Loo Lin School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract Cerebral malaria (CM) is a severe complication caused by Plasmodium falciparum infection, leading to persistent neurological impairments in survivors. To understand the complex mechanisms and investigate advanced diagnostic and treatment strategies targeting human CM, we utilize Plasmodium coatneyi-infected male rhesus macaques, a non-human primate model closely resembling P. falciparum infection in humans. Through differential gene expression analysis, our study demonstrates methylene blue’s efficacy in reversing the detrimental effects of infection on the brainstem. Furthermore, by comparing our brainstem dataset from P. coatneyi-infected Macaca mulatta with two additional transcriptomic datasets (P. coatneyi-infected M. mulatta blood and P. falciparum-infected human blood), we identify nine genes associated with CM severity. Most of these genes are expressed in neutrophils, indicating their potential as blood biomarkers for diagnosing P. falciparum-induced fatal CM. This research highlights the necessity for new CM treatments and reveals promising biomarkers that could improve diagnosis and prognosis in affected individuals.

Date: 2025
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DOI: 10.1038/s41467-025-65552-y

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