Avaliação de fatores preditivos para complicações neurológicas à alta hospitalar e durante seguimento clínico em coorte de crianças e adolescentes com doença neuroinvasiva confirmada por flavivírus

Abstract

Introduction - The flavivirus dengue virus (DENV) and Zika virus (ZIKV) are causes of frequent outbreaks in Brazil. The yellow fever virus (YFV) is endemic in South America and even with a highly effective vaccine, this flavivirus was responsible for an important outbreak between 2016 and 2019 in the southeastern region of Brazil. By definition, neuroinvasive disease confirmed by these flaviviruses, is any acute central or peripheral neurological syndromes, in a patient with viral detection by isolation or polymerase chain reaction (RT-PCR) in blood, CSF or other body fluids. Objective - To characterize the acute neurological manifestations presented by children and adolescents hospitalized with neuroinvasive disease confirmed by the highest incidence of flaviviruses in the country, to evaluate the neurological outcomes at hospital discharge and during outpatient follow-up, as well as to identify risk factors associated with neurological complications, and the time to resolve these complications. Method - This is a prospective study carried out between March 2014 and July 2019. The target populations were patients with neurological manifestations, diagnosed by RT-PCR performed in cerebrospinal fluid (CSF). All CSF samples were collected by doctors, immediately frozen in liquid nitrogen and sent to the Virology Laboratory at UFMG. Patients were followed up clinically to assess the outcomes: death, neurological complications after hospital discharge, use of anti-crisis medication, motor sequelae, insomnia and persistent headache. The time to resolve complications was also assessed. This study was approved by the COEP of UFMG and FHEMIG. Results - 505 patients with neurological manifestations were evaluated, with 91 cases with flavivirus detected in CSF by RT-PCR (18%), with DENV in 14% of patients, ZIKV in 3% and YFV in 1.2% of cases. Among the 91 children initially included, 73 remained for analysis in the study, with 56 DENV, 12 ZIKV and five YFV. Two YFV positive children died during hospitalization and two others were discharged with epileptic anti-crisis medication. Neurological complications were detected at hospital discharge or in the first month after discharge in 20 positive DENV children (39%) and in four ZIKV children (33%). The predictive factors for neurological complications were: detection of YFV in CSF, alteration of CSF cellularity, encephalitis, motor symptoms associated with involvement of the central nervous system (CNS), alteration of the CNS image exam and alteration of the electroencephalogram (EEG ) during hospitalization.The mean time to clinical improvement of the studied outcomes was 2.8 months for DENV positive children (ranging from 0 to 32 months), was 6.3 months for positive ZIKV children (ranging from 0 to 41.3 months) and 2.5 months for positive YFV children (ranging from 0.1 to 10.2 months). There was no statistical difference in relation to the time of evolution (p-value 0.574) between DENV, ZIKV or YFV positive children in the analysis of survival. Conclusion - This was the first prospective study carried out in children and adolescents in Brazil, with confirmed neuroinvasive disease, for the three flaviviruses with the highest incidence in the country. The results found reinforce the importance of the etiological diagnosis by RT-PCR in CSF for the best clinical follow-up of these patients.