Abstract
Dengue (DENV) and chikungunya viruses (CHIKV) cause severe neurological complications, sometimes undiagnosed. Therefore, the use of more accessible neuroinflammatory biomarkers can be advantageous considering their diagnostic and prognostic potential for aggravated clinical outcomes. In this study, we aimed to evaluate neopterin and C-X-C motif chemokine ligand 10 (CXCL-10) in cerebrospinal fluid (CSF) for the diagnosis of neuroinvasive DENV and CHIKV. We analyzed the CSF of 66 patients with neurological disorders, comprising 12 neuroinvasive DENV/CHIKV, 20 inflammatory control (viral, bacterial, and fungal meningitis, and autoimmune disorders), and 24 noninflammatory control (cerebrovascular disease, dementia, neoplasm). There was no difference between the concentration of CSF neopterin in the neuroinvasive DENV/CHIKV and control groups. However, there was a significant difference in the CXCL-10 level when comparing the neuroinvasive DENV/CHIKV group and the non-inflammatory control (p < 0.05). Furthermore, we found a linear correlation between neopterin and CXCL-10 CSF levels in the three groups. For the DENV/CHIKV neuroinvasive diagnosis, the ROC curve showed the best cut-off values for CSF neopterin at 11.23 nmol/L (sensitivity of 67% and specificity of 63%), and for CSF CXCL-10 at 156.5 pg/mL (91.7% sensitivity and specificity). These results show that CXCL-10 in CSF represents an accurate neuroinflammatory biomarker that may contribute to neuroinvasive DENV/CHIKV diagnosis.
Highlights
The chikungunya (CHIKV) and dengue virus (DENV) are arboviruses transmitted to humans through the bites of Aedes mosquito
This study aims to evaluate neopterin and CXCL-10 biomarkers in cerebrospinal fluid (CSF) samples for the diagnosis of neuroinvasive DENV and chikungunya viruses (CHIKV)
According to the results found, the analysis of the inflammatory biomarker CXCL-10 in CSF samples can contribute to the early diagnosis and better understanding of the neuropathogenesis of the DENV and CHIKV arbovirus infection
Summary
The chikungunya (CHIKV) and dengue virus (DENV) are arboviruses transmitted to humans through the bites of Aedes mosquito. The Chikungunya virus belongs to the Alphavirus genus and the Togaviridae family [3]. Both can cause severe neurological complications, such as encephalitis, encephalopathy, meningitis, myelitis, and Guillain–Barré syndrome. Neurological conditions caused by DENV and CHIKV may be due to direct viral action, local inflammatory reaction, or metabolic disturbances [4,5]. CXCL-10 is a low molecular weight cytokine involved in immunity and inflammation processes [6,7]. It plays a major role in recruiting T lymphocytes and natural killer (NK) cells during neuroinflammatory reactions. Among the CXC family chemokines, CXCL-10 is the most important in inducing inflammatory response by leukocytes in several diseases of the nervous system [8,9]
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