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Background: The co-circulation of flaviviruses in tropical regions has led to the hypothesis that immunity generated by a previous dengue infection could promote severe disease outcomes in subsequent infections by heterologous serotypes. This study investigated the influence of antibodies generated by previous Zika infection on the clinical outcomes of dengue infection., Methodology/principal Findings: We enrolled 1,043 laboratory confirmed dengue patients and investigated their prior infection to Zika or dengue. Severe forms of dengue disease were more frequent in patients with previous Zika infection, but not in those previously exposed to dengue., Conclusions/significance: Our findings suggest that previous Zika infection may represent a risk factor for subsequent severe dengue disease, but we did not find evidence of antibody-dependent enhancement (higher viral titer or pro-inflammatory cytokine overexpression) contributing to exacerbation of the subsequent dengue infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Estofolete et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Arbovirus infections are increasingly important causes of disease, whose spectrum of neurological manifestations are not fully known. This study sought to retrospectively assess the incidence of arboviruses in cerebrospinal fluid samples of patients with neurological symptoms to inform diagnosis of central and peripheral nervous system disorders. A total of 255 cerebrospinal fluid (CSF) samples collected from January 2016 to December 2017 were tested for dengue virus (DENV 1-4), Zika virus (ZIKV), and Chikungunya virus (CHIKV) in addition to other neurotropic arboviruses of interest, using genetic and serologic assays. Of the 255 CSF samples analyzed, 3.53% (09/255) were positive for arboviruses presenting mainly as meningitis, encephalitis, and cerebrovascular events, of which ZIKV was detected in 2.74% (7/255), DENV in 0.78% (2/255), in addition to an identified ILHV infection that was described previously. All the cases were detected in adults aged 18 to 74 years old. Our findings highlight the scientific and clinical importance of neurological syndromes associated with arboviruses and demonstrate the relevance of specific laboratory methods to achieve accurate diagnoses as well as highlight the true dimension of these diseases to ultimately improve public health planning and medical case management.

Arthropod-borne viruses (arboviruses) of the genus Flavivirus are distributed globally and cause significant human disease and mortality annually. Flavivirus infections present a spectrum of clinical manifestations, ranging from asymptomatic to severe manifestations, including hemorrhage, encephalitis and death. Herein, we describe 3 case reports of cerebrovascular involvement in patients infected by dengue and Zika viruses in Sao Jose do Rio Preto, São Paulo State, Brazil, a hyperendemic area for arbovirus circulation, including dengue, yellow fever, chikungunya and Saint Louis encephalitis viruses. Our findings highlight the potential threat that unusual clinical manifestations may pose to arbovirus disease management and recovery.