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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Endothelial transcriptomic analysis identifies biomarkers of severe and cerebral malaria
JCI Insight, Volume 8, No. 22, Article e172845, Year 2023
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Description
Malaria can quickly progress from an uncomplicated infection into a life-threatening severe disease. However, the unspecificity of early symptoms often makes it difficult to identify patients at high risk of developing severe disease. Additionally, one of the most feared malaria complications - cerebral malaria - is challenging to diagnose, often resulting in treatment delays that can lead to adverse outcomes. To identify candidate biomarkers for the prognosis and/or diagnosis of severe and cerebral malaria, we have analyzed the transcriptomic response of human brain microvascular endothelial cells to erythrocytes infected with Plasmodium falciparum. Candidates were validated in plasma samples from a cohort of pediatric patients with malaria from Mozambique, resulting in the identification of several markers with capacity to distinguish uncomplicated from severe malaria, the most potent being the metallopeptidase ADAMTS18. Two other biomarkers, Angiopoietin-like-4 and Inhibin-βE were able to differentiate children with cerebral malaria within the severe malaria group, showing increased sensitivity after combination in a biomarker signature. The validation of the predicted candidate biomarkers in plasma of children with severe and cerebral malaria underscores the power of this transcriptomic approach and indicates that a specific endothelial response to P. falciparum-infected erythrocytes is linked to the pathophysiology of severe malaria. © 2023, Gomes et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
Authors & Co-Authors
Gomes, Cláudia
United States, New York
New York University
Varo, Rosauro
Spain, Barcelona
Universitat de Barcelona
Mozambique, Manhica
Centro de Investigação em Saúde de Manhiça Cism
Duran-Frigola, Miquel
United Kingdom, Cambridge
Ersilia Open Source Initiative
Sitoe, Antonio
Mozambique, Manhica
Centro de Investigação em Saúde de Manhiça Cism
Bila, Rubao
Mozambique, Manhica
Centro de Investigação em Saúde de Manhiça Cism
MacHevo, Sónia
Mozambique, Manhica
Centro de Investigação em Saúde de Manhiça Cism
Mayor, A. G.
Spain, Barcelona
Universitat de Barcelona
Mozambique, Manhica
Centro de Investigação em Saúde de Manhiça Cism
Spain, Madrid
Instituto de Salud Carlos Iii
Mozambique, Maputo
Universidade Eduardo Mondlane
Bassat, Quique
Spain, Barcelona
Universitat de Barcelona
Mozambique, Manhica
Centro de Investigação em Saúde de Manhiça Cism
Spain, Madrid
Instituto de Salud Carlos Iii
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Spain, Esplugues de Llobregat
Hospital Sant Joan de Déu Barcelona
Rodríguez, Ana V.
United States, New York
New York University
Statistics
Citations: 1
Authors: 9
Affiliations: 8
Identifiers
Doi:
10.1172/jci.insight.172845
ISSN:
23793708
Research Areas
Health System And Policy
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Study Locations
Mozambique