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<p>Cerebral malaria (CM) is a severe complication caused by <i>Plasmodium falciparum</i> 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 <i>Plasmodium coatneyi</i>-infected male rhesus macaques, a non-human primate model closely resembling <i>P. falciparum</i> 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 <i>P. coatneyi</i>-infected <i>Macaca mulatta</i> with two additional transcriptomic datasets (<i>P. coatneyi</i>-infected <i>M. mulatta</i> blood and <i>P. falciparum-</i>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 <i>P. falciparum</i>-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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月26日

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  • 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,
  • Benoît Malleret

摘要

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.