Current status of the GFAP's potentials in cerebral malaria, a systematic review

Glial fibrillary acidic protein (GFAP) is an astrocytic protein that increases during reactive astrogliosis, a hallmark of neuroinflammation. Cerebral malaria (CM), a severe neurological complication of Plasmodium falciparum infection, is characterized by significant neuroinflammatory processes. This systematic review aimed to assess GFAP expression patterns in CM and evaluate its potential as a diagnostic and prognostic biomarker.

A comprehensive search of PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar was conducted. The review was performed according to PRISMA 2020 guidelines and registered in PROSPERO (CRD42024558265). Of 2,147 records identified, 2,123 studies were excluded after screening. Twenty-four studies (9 human and 15 experimental studies) were included. Data extraction focused on GFAP detection methods, sample types, disease severity, treatment response, and neuropsychological outcomes. Study quality was assessed using the Newcastle-Ottawa Scale for human studies and the SYRCLE Risk of Bias tool for animal studies.

In experimental CM models, GFAP expression was consistently elevated in brain and retinal tissues, correlating with astrocyte activation and neuroinflammation. Human studies showed more variability; several reported no significant increase in plasma GFAP levels in CM patients compared to controls. Variations in sample type, disease severity, patient age, and analytical methods likely contributed to inconsistencies. Neuropsychological outcomes linked to GFAP expression were sparsely and inconsistently reported.

GFAP shows promise as a biomarker of astrocyte activation and neuroinflammation in CM but lacks diagnostic specificity and consistency across clinical studies. Standardized methodologies and longitudinal studies are needed to clarify its temporal dynamics and prognostic relevance in CM.